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How a developing organ robustly coordinates the cellular mechanics and growth to reach a final size and shape remains poorly understood. Through iterations between experiments and model simulations that include a mechanistic description of interkinetic nuclear migration, we show that the local curvature, height, and nuclear positioning of cells in the Drosophila wing imaginal disc are defined by the concurrent patterning of actomyosin contractility, cell-ECM adhesion, ECM stiffness, and interfacial membrane tension. We show that increasing cell proliferation via different growth-promoting pathways results in two distinct phenotypes. Triggering proliferation through insulin signaling increases basal curvature, but an increase in growth through Dpp signaling and Myc causes tissue flattening. These distinct phenotypic outcomes arise from differences in how each growth pathway regulates the cellular cytoskeleton, including contractility and cell-ECM adhesion. The coupled regulation of proliferation and cytoskeletal regulators is a general strategy to meet the multiple context-dependent criteria defining tissue morphogenesis.

Thrombospondin-4 (TSP-4) belongs to the extracellular matrix glycoprotein family of thrombospondins (TSPs). The multidomain, pentameric structure of TSP-4 allows its interactions with numerous extracellular matrix components, proteins and signaling molecules that enable its modulation to various physiological and pathological processes. Characterization of TSP-4 expression under development and pathogenesis of disorders has yielded important insights into mechanisms underlying the unique role of TSP-4 in mediating various processes including cell-cell, cell-extracellular matrix interactions, cell migration, proliferation, tissue remodeling, angiogenesis, and synaptogenesis. Maladaptation of these processes in response to pathological insults and stress can accelerate the development of disorders including skeletal dysplasia, osteoporosis, degenerative joint disease, cardiovascular diseases, tumor progression/metastasis and neurological disorders. Overall, the diverse functions of TSP-4 suggest that it may be a potential marker or therapeutic target for prognosis, diagnosis, and treatment of various pathological conditions upon further investigations. This review article highlights recent findings on the role of TSP-4 in both physiological and pathological conditions with a focus on what sets it apart from other TSPs.

Approximately a quarter of the human genome consists of gene deserts, large regions devoid of genes often located adjacent to developmental genes and thought to contribute to their regulation. However, defining the regulatory functions embedded within these deserts is challenging due to their large size. Here, we explore the cis-regulatory architecture of a gene desert flanking the Shox2 gene, which encodes a transcription factor indispensable for proximal limb, craniofacial, and cardiac pacemaker development. We identify the gene desert as a regulatory hub containing more than 15 distinct enhancers recapitulating anatomical subdomains of Shox2 expression. Ablation of the gene desert leads to embryonic lethality due to Shox2 depletion in the cardiac sinus venosus, caused in part by the loss of a specific distal enhancer. The gene desert is also required for stylopod morphogenesis, mediated via distributed proximal limb enhancers. In summary, our study establishes a multi-layered role of the Shox2 gene desert in orchestrating pleiotropic developmental expression through modular arrangement and coordinated dynamics of tissue-specific enhancers.

Understanding the mechanisms of the cellular aging processes is crucial for attempting to extend organismal lifespan and for studying age-related degenerative diseases. Yeast cells divide through budding, providing a classical biological model for studying cellular aging. With their powerful genetics, relatively short cell cycle, and well-established signaling pathways also found in animals, yeast cells offer valuable insights into the aging process. Recent experiments suggested the existence of two aging modes in yeast characterized by nucleolar and mitochondrial declines, respectively. By analyzing experimental data, this study shows that cells evolving into those two aging modes behave differently when they are young. While buds grow linearly in both modes, cells that consistently generate spherical buds throughout their lifespan demonstrate greater efficacy in controlling bud size and growth rate at young ages. A three-dimensional multiscale chemical-mechanical model was developed and used to suggest and test hypothesized impacts of aging on bud morphogenesis. Experimentally calibrated model simulations showed that during the early stage of budding, tubular bud shape in one aging mode could be generated by locally inserting new materials at the bud tip, a process guided by the polarized Cdc42 signal. Furthermore, the aspect ratio of the tubular bud could be stabilized during the late stage as observed in experiments in this work. The model simulation results suggest that the localization of new cell surface material insertion, regulated by chemical signal polarization, could be weakened due to cellular aging in yeast and other cell types, leading to the change and stabilization of the bud aspect ratio.

The development of ectodermal organs begins with the formation of a stratified epithelial placode that progressively invaginates into the underlying mesenchyme as the organ takes its shape. Signaling by secreted molecules is critical for epithelial morphogenesis, but how that information leads to cell rearrangement and tissue shape changes remains an open question. Using the mouse dentition as a model, we first establish that non-muscle myosin II is essential for dental epithelial invagination and show that it functions by promoting cell-cell adhesion and persistent convergent cell movements in the suprabasal layer. Shh signaling controls these processes by inducing myosin II activation via AKT. Pharmacological induction of AKT and myosin II can also rescue defects caused by the inhibition of Shh. Together, our results support a model in which the Shh signal is transmitted through myosin II to power effective cellular rearrangement for proper dental epithelial invagination.

The Hedgehog (Hh) pathway plays a crucial role in embryonic development, acting both as a morphogenic signal that organizes tissue formation and a potent mitogenic signal driving cell proliferation. Dysregulated Hh signaling leads to various developmental defects in the brain. This article aims to review the roles of Hh signaling in the development of the neocortex in the mammalian brain, focusing on its regulation of neural progenitor proliferation and neuronal production. The review will summarize studies on genetic mouse models that have targeted different components of the Hh pathway, such as the ligand Shh, the receptor Ptch1, the GPCR-like transducer Smo, the intracellular transducer Sufu, and the three Gli transcription factors. As key insights into the Hh signaling transduction mechanism were obtained from mouse models displaying neural tube defects, this review will also cover some studies on Hh signaling in neural tube development. The results from these genetic mouse models suggest an intriguing hypothesis that elevated Hh signaling may play a role in the gyrification of the brain in certain species. Additionally, the distinctive production of GABAergic interneurons in the dorsal cortex in the human brain may also be linked to the extension of Hh signaling from the ventral to the dorsal brain region. Overall, these results suggest key roles of Hh signaling as both a morphogenic and mitogenic signal during the forebrain development and imply the potential involvement of Hh signaling in the evolutionary expansion of the neocortex.

Large-scale cell flow characterizes gastrulation in animal development. In amniote gastrulation, particularly in avian gastrula, a bilateral vortex-like counter-rotating cell flow, called 'polonaise movements', appears along the midline. Here, through experimental manipulations, we addressed relationships between the polonaise movements and morphogenesis of the primitive streak, the earliest midline structure in amniotes. Suppression of the Wnt/planar cell polarity (PCP) signaling pathway maintains the polonaise movements along a deformed primitive streak. Mitotic arrest leads to diminished extension and development of the primitive streak and maintains the early phase of the polonaise movements. Ectopically induced Vg1, an axis-inducing morphogen, generates the polonaise movements, aligned to the induced midline, but disturbs the stereotypical cell flow pattern at the authentic midline. Despite the altered cell flow, induction and extension of the primitive streak are preserved along both authentic and induced midlines. Finally, we show that ectopic axis-inducing morphogen, Vg1, is capable of initiating the polonaise movements without concomitant PS extension under mitotic arrest conditions. These results are consistent with a model wherein primitive streak morphogenesis is required for the maintenance of the polonaise movements, but the polonaise movements are not necessarily responsible for primitive streak morphogenesis. Our data describe a previously undefined relationship between the large-scale cell flow and midline morphogenesis in gastrulation.

Angiogenesis is a morphogenic process resulting in the formation of new blood vessels from pre-existing ones, usually in hypoxic micro-environments. The initial steps of angiogenesis depend on robust differentiation of oligopotent endothelial cells into the Tip and Stalk phenotypic cell fates, controlled by NOTCH-dependent cell-cell communication. The dynamics of spatial patterning of this cell fate specification are only partially understood. Here, by combining a controlled experimental angiogenesis model with mathematical and computational analyses, we find that the regular spatial Tip-Stalk cell patterning can undergo an order-disorder transition at a relatively high input level of a pro-angiogenic factor VEGF. The resulting differentiation is robust but temporally unstable for most cells, with only a subset of presumptive Tip cells leading sprout extensions. We further find that sprouts form in a manner maximizing their mutual distance, consistent with a Turing-like model that may depend on local enrichment and depletion of fibronectin. Together, our data suggest that NOTCH signaling mediates a robust way of cell differentiation enabling but not instructing subsequent steps in angiogenic morphogenesis, which may require additional cues and self-organization mechanisms. This analysis can assist in further understanding of cell plasticity underlying angiogenesis and other complex morphogenic processes.

Although the mechanisms of molluscan shell growth have been studied using mathematical models, little is known about the molecular basis underpinning shell morphogenesis. Here, we performed Wnt activation experiments to elucidate the potential roles of Wnt signaling in the shell growth of Lymnaea stagnalis. In general, we observed following three types of shell malformations in both dose- and developmental stage-dependent manners: (i) cap-shaped shell, (ii) cap-shaped shell with hydropic soft tissues, and (iii) compressed shell with a smaller number of coiling. We analyzed the morphologies of these malformed shells using the growing tube model, revealing that the compressed malformations show significantly larger values for T (torsion), with no significant changes in the values for the remaining parameters E (expansion) and C (curvature). We also found that cap-shaped malformations have significantly larger values for E, suggesting that the effects of BIO on shell formation may change during growth. Since the changes in T and/or E parameter values can greatly alter the shell morphologies from a planispiral or a cap-shaped one to various three-dimensional helices, changes in shell developmental processes possibly controlled by Wnt signaling may account for at least a part of the evolution of diverse shell forms in molluscs. [ABSTRACT FROM AUTHOR]

Taking 4-year-old Rosa roxburghii seedlings as the research object, the effects of glyphosate in orchards on the nutritional growth, leaf structure, photosynthetic characteristics, fluorescence characteristics and fruits were studied by soil application of glyphosate. The results show that new leaf morphology was deformed and yellowed, stomatal density and stomatal index were significantly decreased, MDA content was increased, and SOD, CAT and LOX activities were significantly increased after 15 days of glyphosate treatment. PN, GS, Fv/Fm, ABS/RC, TRo/RC, ETo/RC and DIo/RC of new leaves were significantly reduced with increasing glyphosate concentrations. New leaf photosynthetic organ development and photosynthetic pigment accumulation were affected under glyphosate, resulting in inhibition of photosynthesis, leading to a decrease in photosynthetic rate and ultimately affecting fruit development. The protective enzyme activity of new leaves was activated after glyphosate spraying, thereby enhancing its adaptability to adversity, while damage to PSII was reduced by increasing the energy dissipated through heat dissipation and reducing excess excitation energy under low dose glyphosate treatment. The adaptability of new leaf cell membranes could be improved, and thus the damage caused by glyphosate was mitigated in Rosa roxburghii orchards when glyphosate was applied at concentrations of less than 1.84 kg.ha-1. [ABSTRACT FROM AUTHOR]

Formation of fluid-filled lumina by epithelial tissues is essential for organ development. How cells control the hydraulic and cortical forces to control lumen morphology is not well understood. Here, we quantified the mechanical role of tight junctions in lumen formation using MDCK-II cysts. We found that the paracellular ion barrier formed by claudin receptors is not required for the hydraulic inflation of a lumen. However, the depletion of the zonula occludens scaffold resulted in lumen collapse and folding of apical membranes. Combining quantitative measurements of hydrostatic lumen pressure and junctional tension with modeling enabled us to explain lumen morphologies from the pressure-tension force balance. Tight junctions promote lumen inflation by decreasing cortical tension via the inhibition of myosin. In addition, our results suggest that excess apical area contributes to lumen opening. Overall, we provide a mechanical understanding of how epithelial cells use tight junctions to modulate tissue and lumen shape. [Display omitted] • Depletion of ZO scaffold causes lumen collapse and apical membrane folding • The claudin permeability barrier is not necessary for hydraulic lumen inflation • Tight junctions promote lumen inflation by decreasing cortical tension • Lumen shape controlled by pressure-tension force balance and apical area constraints Mukenhirn et al. show that epithelial cells use tight junctions to control lumen shape, and the depletion of the tight junction scaffold leads to lumen collapse and increased cortical tension. Claudin-depleted MDCK-II cysts maintain lumen pressure and shape despite high ion permeability. [ABSTRACT FROM AUTHOR]

Hox transcription factors play crucial roles in organizing developmental patterning across metazoa, but how these factors trigger regional morphogenesis has largely remained a mystery. In the developing gut, Hox genes help demarcate identities of intestinal subregions early in embryogenesis, which ultimately leads to their specialization in both form and function. Although the midgut forms villi, the hindgut develops sulci that resolve into heterogeneous outgrowths. Combining mechanical measurements of the embryonic chick intestine and mathematical modeling, we demonstrate that the posterior Hox gene HOXD13 regulates biophysical phenomena that shape the hindgut lumen. We further show that HOXD13 acts through the transforming growth factor β (TGF-β) pathway to thicken, stiffen, and promote isotropic growth of the subepithelial mesenchyme—together, these features lead to hindgut-specific surface buckling. TGF-β, in turn, promotes collagen deposition to affect mesenchymal geometry and growth. We thus identify a cascade of events downstream of positional identity that direct posterior intestinal morphogenesis. [Display omitted] • Mechanical properties define epithelial buckling in the developing chick intestine • HOXD13 promotes hindgut mechanics through increased mesenchymal TGF-β signaling • Hindgut and ectopic midgut HOXD13- expressing smooth muscle upregulates INHBA • Mesenchymal TGF-β activation tunes mechanics via extracellular matrix remodeling Gill et al. mechanistically link HOXD13 expression to morphogenesis of the chick hindgut epithelium. HOXD13 activity within smooth muscle induces INHBA expression, which causes adjacent mesenchymal cells to remodel extracellular matrix (ECM) in response to TGF-β upregulation, thus promoting the biomechanical parameters that define the hindgut morphological trajectory. [ABSTRACT FROM AUTHOR]

Minipuberty is the second phase of physiological activation of the reproductive axis, playing a role in the postnatal development of sexual organs. The course of female minipuberty was found to be affected by low maternal vitamin D status and hypothyroidism during pregnancy. The aim of the current study was to assess the hormonal profile and the size of sexual organs in daughters of mothers with gestational diabetes mellitus. The study included three matched groups of infant girls: daughters of healthy women without metabolic disorders during pregnancy (group 1), daughters of women with poorly controlled gestational diabetes mellitus (group 2), and daughters of women with gestational diabetes mellitus adequately controlled during pregnancy (group 3). Urinary levels of gonadotropins, salivary levels of estradiol, testosterone, DHEA-S and progesterone, ovarian volume, uterine length and breast diameter were measured from postnatal month 1 to postnatal month 18. Concentrations of FSH, LH and estradiol were higher, while concentration of progesterone was lower in group 2 than in the remaining groups. There were no between-group differences in concentrations of testosterone and DHEA-S. Levels of LH, FSH, estradiol and progesterone correlated with maternal whole-blood levels of glycated hemoglobin. Group 2 was also characterized by the longest detection periods for LH and estradiol. Ovarian volume, uterine length and breast diameter were greater in group 1 than in the remaining two groups. Over the entire observation period, there were no differences in hormone levels and sizes of the sexual organs between groups 1 and 3. The obtained results suggest that poorly controlled, but not well controlled, gestational diabetes mellitus affects the course of female minipuberty. [ABSTRACT FROM AUTHOR]

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a novel betacoronavirus, is the causative agent of COVID-19, which has caused economic and social disruption worldwide. To date, many drugs and vaccines have been developed for the treatment and prevention of COVID-19 and have effectively controlled the global epidemic of SARS-CoV-2. However, SARS-CoV-2 is highly mutable, leading to the emergence of new variants that may counteract current therapeutic measures. Electron microscopy (EM) is a valuable technique for obtaining ultrastructural information about the intracellular process of virus replication. In particular, EM allows us to visualize the morphological and subcellular changes during virion formation, which would provide a promising avenue for the development of antiviral agents effective against new SARS-CoV-2 variants. In this review, we present our recent findings using transmission electron microscopy (TEM) combined with electron tomography (ET) to reveal the morphologically distinct types of SARS-CoV-2 particles, demonstrating that TEM and ET are valuable tools for visually understanding the maturation status of SARS-CoV-2 in infected cells. This review also discusses the application of EM analysis to the evaluation of genetically engineered RNA viruses. [ABSTRACT FROM AUTHOR]

Myelomeningocele (MMC) is a congenital birth defect of the spine and spinal cord, commonly treated clinically through prenatal or postnatal surgery by repairing the unclosed spinal canal. Having previously developed a PLA/PCL polymer smart patch for this condition, we aim to further expand the potential therapeutic options by providing additional cellular and biochemical support in addition to its mechanical properties. Bone morphogenetic proteins (BMPs) are a large class of secreted factors that serve as modulators of development in multiple organ systems, including the CNS. We hypothesize that our smart patch mitigates the astrogenesis induced, at least partly, by increased BMP activity during MMC. To test this hypothesis, neural stem or precursor cells were isolated from rat fetuses and cultured in the presence of Noggin, an endogenous antagonist of BMP action, with recombinant BMPs. We found that the developed PLA/PCL patch not only serves as a biocompatible material for developing neural stem cells but was also able to act as a carrier for BMP–Notch pathway inhibitor Noggin, effectively minimizing the effect of BMP2 or BMP4 on NPCs cultured with the Noggin-loaded patch. [ABSTRACT FROM AUTHOR]

The role of long intergenic noncoding RNAs (lincRNAs) in fetal development has emerged as a significant area of study, challenging the traditional protein-centric view of gene expression. While messenger RNAs (mRNAs) have long been recognized for their role in encoding proteins, recent advances have illuminated the critical functions of lincRNAs in various biological processes. Initially identified through high-throughput sequencing technologies, lincRNAs are transcribed from intergenic regions between protein-coding genes and exhibit unique regulatory functions. Unlike mRNAs, lincRNAs are involved in complex interactions with chromatin and chromatin-modifying complexes, influencing gene expression and chromatin structure. LincRNAs are pivotal in regulating tissue-specific development and embryogenesis. For example, they are crucial for proper cardiac, neural, and reproductive system development, with specific lincRNAs being associated with organogenesis and differentiation processes. Their roles in embryonic development include regulating transcription factors and modulating chromatin states, which are essential for maintaining developmental programs and cellular identity. Studies using RNA sequencing and genetic knockout models have highlighted the importance of lincRNAs in processes such as cell differentiation, tissue patterning, and organ development. Despite their functional significance, the comprehensive annotation and understanding of lincRNAs remain limited. Ongoing research aims to elucidate their mechanisms of action and potential applications in disease diagnostics and therapeutics. This review summarizes current knowledge on the functional roles of lincRNAs in fetal development, emphasizing their contributions to tissue-specific gene regulation and developmental processes. [ABSTRACT FROM AUTHOR]

Cell migration is a fundamental and functional cellular process, influenced by a complex microenvironment consisting of different cells and extracellular matrix. Recent research has highlighted that, besides biochemical cues from the microenvironment, physical cues can also greatly alter cellular behavior. However, due to the complexity of the microenvironment, little is known about how the physical interactions between migrating cells and surrounding microenvironment instructs cell movement. Here, we explore various examples of three-dimensional microenvironment reconstruction models in vitro and describe how the physical interplay between migrating cells and the neighboring microenvironment controls cell behavior. Understanding this mechanical cooperation will provide key insights into organ development, regeneration, and tumor metastasis. [ABSTRACT FROM AUTHOR]

Chronic allograft dysfunction (CAD) poses a significant challenge in kidney transplantation, with renal vascular endothelial‐to‐mesenchymal transition (EndMT) playing a vital role. While renal vascular EndMT has been verified as an important contributing factor to renal allograft interstitial fibrosis/tubular atrophy in CAD patients, its underlying mechanisms remain obscure. Currently, Src activation is closely linked to organ fibrosis development. Single‐cell transcriptomic analysis in clinical patients revealed that Src is a potential pivotal mediator in CAD progression. Our findings revealed a significant upregulation of Src which closely associated with EndMT in CAD patients, allogeneic kidney transplanted rats and endothelial cells lines. In vivo, Src inhibition remarkably alleviate EndMT and renal allograft interstitial fibrosis in allogeneic kidney transplanted rats. It also had a similar antifibrotic effect in two endothelial cell lines. Mechanistically, the knockout of Src resulted in an augmented AMBRA1‐mediated mitophagy in endothelial cells. We demonstrate that Src knockdown upregulates AMBRA1 level and activates mitophagy by stabilizing Parkin's ubiquitination levels and mitochondrial translocation. Subsequent experiments demonstrated that the knockdown of the Parkin gene inhibited mitophagy in endothelial cells, leading to increased production of Interleukin‐6, thereby inducing EndMT. Consequently, our study underscores Src as a critical mediator of renal vascular EndMT and allograft interstitial fibrosis, exerting its impact through the regulation of AMBRA1/Parkin‐mediated mitophagy. [ABSTRACT FROM AUTHOR]

Melatonin was discovered in plants in 1995, and so-called phytomelatonin. Its characteristic qualities as an antioxidant molecule and with amphiphilic nature make it an excellent candidate to use in plant biotechnological techniques. In plant physiology, melatonin has demonstrated with multiple studies great possibilities of application in crop improvement in aspects such as germination, rooting, plant growth, leaf-senescence, floration, fruit-set, parthenocarpy, fruit ripening and cut flower conservation, among others. In this work, we reviewed many studies on the possible role of melatonin to improve the different plant tissue culture goals, among them: the role of melatonin in callus culture induction and its effects in plant biomass production; the possible action of melatonin as an inductor or elicitor of different secondary metabolite generation in in vitro cultures; the interesting possibilities of melatonin as a protective agent (safener) against abiotic stressors present in in vitro cultures; the potential of melatonin in regulating plant organogenesis, modulating shooting/rooting responses; at last, the studies on the relevant role of melatonin in plant material cryopreservation and the improvement of cell transformation using A. tumefaciens have been discussed. [ABSTRACT FROM AUTHOR]

Background: Pineoblastoma (PB) represents a great challenge for clinical management due to lack of a specific therapeutic regimen. This study aims to identify relevant prognostic factors and potential treatment targets by mining public databases. Methods: The clinical characteristics and survival data of PB patients were obtained from the SEER database between 2000 and 2019 for Cox regression analysis and nomogram construction. The PB's DNA methylation data was acquired from two GEO datasets, GSE133801 and GSE215240, for bioinformatics analysis. Results: Of 383 PB patients, Cox univariate analysis unveiled that male gender (p = 0.017), age younger than 3 years at diagnosis (p < 0.001) and absence of radiotherapy (p < 0.001) correlated with poorer overall survival (OS), the subsequent multivariate analysis confirmed sex (p = 0.036), age (p < 0.001) and radiotherapy (p = 0.005) as independent prognostic factors for OS. A nomogram showed robust predictive accuracy as evidenced by AUC values (1-year OS: 0.774, 3-year OS: 0.692, 5-year OS: 0.643). DNA methylation analysis observed tumor hypomethylation, notably in promoter regions. Later, the GO enrichment analysis of aberrantly methylated genes indicated associations with embryonic organ development, cellular membrane composition and DNA-binding transcription, while KEGG analysis revealed enrichment in tumor-associated MAPK, calcium and RAS signaling pathways. Conclusions: The prognosis of PB is closely associated with sex, age and receipt of radiotherapy, potentially linked to aberrations in the RAS and MAPK signaling pathways. The individual case suggests that dasatinib and trametinib are potential targeted therapies for improving PB prognosis. [ABSTRACT FROM AUTHOR]

Currently available guidelines on the daily formula milk requirements of infants are based on the needs of infants with their growth pattern following the 50th percentile of the weight-for-age growth curve. Hence, current recommendations may not thoroughly detail the needs of infants across the broad spectrum of body weight percentiles. This study aimed to provide stratified recommendations for daily formula milk intake of fully formula-fed infants, across different weight-for-age categories from 0 to 4 months. At first, theoretical age- and gender-specific weight ranges were constructed for infants across five pre-defined weight-for-length percentile categories of the WHO growth standard. Thereafter, total daily energy requirements for each category were calculated and converted to daily formula milk needs. Subsequently, these stratified age- and weight-formula milk recommendations were compared to actual daily and relative formula milk of infants in these categories, retrieved from pooled individual infant formula milk intake data derived from 13 clinical intervention trials. A fitted regression model was used to evaluate differences in volume intakes across body weight categories as well as between theoretically derived and actual intake values. Median daily formula milk volume intake (ml/day) of infants differed significantly across the increasing weight-for-age categories at each time point, with significant differences between small and large infants. Interestingly, the relative daily formula milk volume intake (ml/kg/day) was higher for smaller infants compared to larger infants. The mean daily and relative formula milk intakes demonstrated the same pattern based on theoretical calculations as well as for the actual formula milk intake values retrieved from 13 pooled clinical intervention trials. Conclusions: Based on theoretical calculations and actual formula intake data, we conclude that larger infants require a significantly higher daily formula milk intake than smaller infants, and we postulate that infants could benefit from more tailored formula milk intake recommendations. What is Known: • Adequate energy intake during the infancy period is crucial to support optimal growth and organ development, with the potential for long-lasting health effects. • Current available guidelines on the daily formula milk requirements of infants are based on the needs of infants with their growth pattern following the 50th percentile of the weight-for-age growth curve. What is New: • Based on using both theoretical calculations and actual formula intake data, larger infants require a significantly higher daily formula milk intake than smaller infants. • Exclusive formula-fed infants could benefit from more tailored formula milk intake recommendations, in early infancy. [ABSTRACT FROM AUTHOR]

An intense black pigmented halotolerant yeast GUBPC1, was obtained from the solar salterns of Nerul, Goa-India. The isolate could tolerate 0 to 20 % NaCl. FE-SEM analysis revealed its polymorphic nature, exhibiting oval cells at higher salt concentrations and filamentous spindle like shapes at lower concentrations. Initially, the cells appear oval, yeast like in shape but gradually after 15 days of incubation, it becomes elongated and undergoes budding, exhibiting various budding patterns, from single polar bud to bipolar buds with annellidic ring, to lateral buds and eventually forming filamentous hyphae. The intracellular black pigment was identified as melanin based on ultraviolet–visible spectroscopy analysis. The molecular identification of the culture showed closest similarity with Hortaea werneckii. Plant polymer-degrading enzymatic activities such as cellulase, laccase, chitinase, xylanase, pectinase, amylase and protease were exhibited by the isolate GUBPC1. To further understand and explore its biotechnological potential, we performed whole-genome sequencing and analysis. The obtained genome size was 26.93 Mb with 686 contigs and a GC content of 53.24 %. We identified 9383 protein-coding genes, and their functional annotation revealed the presence of 435 CAZyme genes and 16 functional genes involved in secondary metabolite synthesis, thus providing a basis for its potential value in various biotechnological applications. [ABSTRACT FROM AUTHOR]

The ectoderm is the outermost of the three germ layers of the early embryo that arise during gastrulation. Once the germ layers are established, the complex interplay of cellular proliferation, differentiation, and migration results in organogenesis. The ectoderm is the progenitor of both the surface ectoderm and the neural ectoderm. Notably, the surface ectoderm develops into the epidermis and its associated appendages, nails, external exocrine glands, olfactory epithelium, and the anterior pituitary. Specification, development, and homeostasis of these organs demand a tightly orchestrated gene expression program that is often dictated by epigenetic regulation. In this review, we discuss the recent discoveries that have highlighted the importance of chromatin regulatory mechanisms mediated by transcription factors, histone and DNA modifications that aid in the development of surface ectodermal organs and maintain their homeostasis post-development. [Display omitted] • Chromatin regulatory mechanisms are inherently important for surface ectoderm organ development and homeostasis. • These mechanisms are mediated by transcription factors, histone, and DNA modifiers. • Recent studies have highlighted how signaling effectors, TFs, and chromatin modifiers converge to regulate key processes essential for tissue identity. [ABSTRACT FROM AUTHOR]

Thyroid hormone regulates the rate of testis maturation in mammals. Manipulations of thyroid hormone levels in neonatal animals affect various aspects of testis biology. However, there have been no studies examining the effects of thyroid hormone on the rete testis (RT). Here, we used animal models of neonatal hyperthyroidism (injections of triiodothyronine, or T3) and hypothyroidism (goitrogen 6-propyl-2-thiouracil [PTU] treatment) and found that higher levels of thyroid hormone accelerate RT development, while lower levels of thyroid hormone delay it. T3 and PTU treatments influence RT size, proliferation of RT cells, and expression of DMRT1 and androgen receptor in the RT. T3 supplementation accelerates RT development in an organ testicular culture, which indicates the local action of thyroid hormone. Additionally, it was found that follicle-stimulating hormone could be involved in the regulation both of RT proliferation and RT size. The fact that RT cells in a cell culture do not respond to T3 suggests indirect action of thyroid hormone on the RT in vivo or the loss of the responsiveness to the hormone in vitro. [ABSTRACT FROM AUTHOR]

Bamboo plants have erratic flowering habits with a long vegetative growth and an uncertain flowering cycle. The process of floral transition has always been one of the hot and intriguing topics in bamboo developmental biology. As master modulators of gene expression at the post-transcriptional level, miRNAs play a crucial role in regulating reproductive growth, especially in floral transition of flowering plants. Pleioblastus pygmaeus is a kind of excellent ground cover ornamental bamboo species. In this study, we performed miRNA expression profiling of the shoot buds and flower buds from the bamboo species, to investigate flowering-related miRNAs in bamboo plants. A total of 179 mature miRNAs were identified from P. pygmaeus, including 120 known miRNAs and 59 novel miRNAs, of which 96 (61 known miRNAs and 35 novel miRNAs) were differentially expressed in the shoots at different growth stages. Based on target gene (TG) prediction, a total of 2099 transcription factors (TFs) were annotated to be TGs of the 96 differentially expressed miRNAs (DEMs), corresponding to 839 recordings of DEM-TF pairs. In addition, we identified 23 known DEMs involved in flowering and six known miRNAs related to floral organ development based on previous reports. Among these, there were 11 significantly differentially expressed miRNAs, with 124 TF targets corresponding to 132 DEM-TF pairs in P. pygmaeus. In particular, we focused on the identification of miR156a-SPL (SQUAMOSA Promoter-Binding protein-Like) modules in the age pathway, which are well-known to regulate the vegetative-to-reproductive phase transition in flowering plants. A total of 36 TF targets of miR156a were identified, among which there were 11 SPLs. The Dual-Luciferase transient expression assay indicated miR156a mediated the repression of the PpSPL targets in P. pygmaeus. The integrated analysis of miRNAs and TGs at genome scale in this study provides insight into the essential roles of individual miRNAs in modulating flowering transition through regulating TF targets in bamboo plants. [ABSTRACT FROM AUTHOR]

Fetal and neonatal development is a critical period for the establishment of the future metabolic health and disease risk of an individual. Both maternal undernutrition and overnutrition can result in abnormal fetal organ development resulting in inappropriate birth size, child and adult obesity, and increased risk of Type 2 diabetes and cardiovascular diseases. Inappropriate adaptive changes to the maternal pancreas, placental function, and the development of the fetal pancreas in response to nutritional stress during pregnancy are major contributors to a risk trajectory in the offspring. This interconnected maternal-placental-fetal metabolic axis is driven by endocrine signals in response to the availability of nutritional metabolites and can result in cellular stress and premature aging in fetal tissues and the inappropriate expression of key genes involved in metabolic control as a result of long-lasting epigenetic changes. Such changes result is insufficient pancreatic beta-cellmass and function, reduced insulin sensitivity in target tissues such as liver and white adipose and altered development of hypothalamic satiety centres and in basal glucocorticoid levels. Whilst interventions in the obese mother such as dieting and increased exercise, or treatment with insulin or metformin in mothers who develop gestational diabetes, can improve metabolic control and reduce the risk of a large-for-gestational age infant, their effectiveness in changing the adverse metabolic trajectory in the child is as yet unclear. [ABSTRACT FROM AUTHOR]

Mesothelial cells, in the outermost layer of internal organs, are essential for both organ development and homeostasis. Although the parietal mesothelial cell is the primary origin of mesothelioma that may highjack developmental signaling, the signaling pathways that orchestrate developing parietal mesothelial progenitor cell (MPC) behaviors, such as MPC pool expansion, maturation, and differentiation, are poorly understood. To address it, we established a robust protocol for culturing WT1+ MPCs isolated from developing pig and mouse parietal thorax. Quantitative qPCR and immunostaining analyses revealed that BMP4 facilitated MPC differentiation into smooth muscle cells (SMCs). In contrast, FGF2 significantly promoted MPC progenitor pool expansion but blocked the SMC differentiation. BMP4 and FGF2 counterbalanced these effects, but FGF2 had the dominant impact in the long-term culture. A Wnt activator, CHIR99021, was pivotal in MPC maturation to CALB2+ mesothelial cells, while BMP4 or FGF2 was limited. Our results demonstrated central pathways critical for mesothelial cell behaviors. [ABSTRACT FROM AUTHOR]

Plants have evolved a remarkable ability to sense and respond to changes in photoperiod, allowing adjustments to their growth and development based on seasonal and environmental cues. The floral transition is a pivotal stage in plant growth and development, signifying a shift from vegetative to reproductive growth. CONSTANS (CO), a central photoperiodic response factor conserved in various plants, mediates day‐length signals to control the floral transition, although its mechanisms of action vary among plants with different day‐length requirements. In addition, recent studies have uncovered roles for CO in organ development and stress responses. These pleiotropic roles in model plants and crops make CO a potentially fruitful target for molecular breeding aimed at modifying crop agronomic traits. This review systematically traces research on CO, from its discovery and functional studies to the exploration of its regulatory mechanisms and newly discovered functions, providing important insight into the roles of CO and laying a foundation for future research. [ABSTRACT FROM AUTHOR]

Chondrocyte columns, which are a hallmark of growth plate architecture, play a central role in bone elongation. Columns are formed by clonal expansion following rotation of the division plane, resulting in a stack of cells oriented parallel to the growth direction. In this work, we analyzed hundreds of Confetti multicolor clones in growth plates of mouse embryos using a pipeline comprising 3D imaging and algorithms for morphometric analysis. Surprisingly, analysis of the elevation angles between neighboring pairs of cells revealed that most cells did not display the typical stacking pattern associated with column formation, implying incomplete rotation of the division plane. Morphological analysis revealed that although embryonic clones were elongated, they formed clusters oriented perpendicular to the growth direction. Analysis of growth plates of postnatal mice revealed both complex columns, composed of ordered and disordered cell stacks, and small, disorganized clusters located in the outer edges. Finally, correlation between the temporal dynamics of the ratios between clusters and columns and between bone elongation and expansion suggests that clusters may promote expansion, whereas columns support elongation. Overall, our findings support the idea that modulations of division plane rotation of proliferating chondrocytes determines the formation of either clusters or columns, a multifunctional design that regulates morphogenesis throughout pre-and postnatal bone growth. Broadly, this work provides a new understanding of the cellular mechanisms underlying growth plate activity and bone elongation during development. [ABSTRACT FROM AUTHOR]

Tissue interfaces are essential for development and their disruption often leads to diseases such as tumor invasion. Here, we combine experiments, theoretical modeling, and numerical simulations to quantify the morphodynamics of interface in a biphasic system composed of Madin Darby canine kidney (MDCK) and mouse myoblast (C2C12) cells. We show that cellular activity regulates the interface morphodynamics and drives wave propagation along the interface. Based on the dispersion relationship, we identify that the wave dynamics results from the activity-mediated instability of the interface and coherent flow. It is found that the topological defects accumulate around and destabilize the interface and +1/2 topological defects are more likely to aggregate in MDCK cell clusters. A biphasic active nematic theory is employed to reproduce our experimental observations and decipher the underlying mechanisms. These findings provide physical insights into the interfacial evolution that could be implicated in tissue morphogenesis and tumor invasion. Interfaces are ubiquitous in living systems and play pivotal roles in physiological and pathological processes. The authors combine experiments and numerical simulations to investigate morphodynamics of the interface between dissimilar cell aggregations. [ABSTRACT FROM AUTHOR]

Recent advancements in 3D tissue engineering and organ‐on‐a‐chip systems have revolutionized biomedical research by providing sophisticated platforms that mimic complex physiological environments. This review explores various techniques in 3D printing, including bioprinting materials, laser‐induced forward transfer, ink‐jet systems, and microextrusion methods, highlighting their roles in fabricating intricate tissue constructs. Physical and biochemical characterization methods for assessing these engineered tissues on microchips are discussed in detail, emphasizing their importance in accurately replicating physiological conditions. The review further delves into the development of multiple organ and single organ‐on‐a‐chip systems. It covers two‐organ, three‐organ, and four‐organ platforms, as well as individual systems such as pancreas‐on‐a‐chip, kidney‐on‐a‐chip, liver‐on‐a‐chip, lung‐on‐a‐chip, blood–brain barrier‐on‐a‐chip, heart‐on‐a‐chip, breast cancer‐on‐a‐chip, gut‐on‐a‐chip, and blood vessels‐on‐a‐chip. Each section addresses the unique challenges and advancements associated with these models, providing insights into their potential applications in drug testing, disease modelling, and personalized medicine. In conclusion, the article discusses current challenges and offers perspectives on future directions in 3D tissue engineering and organ‐on‐a‐chip technology, highlighting the transformative impact of these systems on biomedical research and healthcare. [ABSTRACT FROM AUTHOR]

As the most advanced non‐viral delivery system, lipid nanoparticles (LNPs) were approved by the FDA, propelling the advancements of gene therapy. However, their clinical applications are hampered by the potential immunogenicity of the lipid components that trigger immune‐related adverse events, like inflammation and allergy. Herein, we formulate various dLNPs with diminished immunogenicity by incorporating dexamethasone (Dex) into liver‐, spleen‐, and lung‐targeting LNPs formulations that exhibit excellent abilities to target specific organs and deliver various types of RNA, such as mRNA and siRNA. In vivo investigations demonstrate unparalleled advantages in safety as compared to conventional LNPs, showing promising potential in the development of RNA therapeutics. Intriguingly, the encapsulation of runt‐related transcription factor‐1 siRNA (siRUNX1) into lung‐targeting dLNPs (dLNPs@siRUNX1) demonstrates remarkable advantages in the treatment of pulmonary fibrosis through the synergy of gene therapy and drug therapy. This research establishes secure and universal platforms for the precise delivery of nucleic acid therapeutics, showcasing promising clinical applications in gene therapy. [ABSTRACT FROM AUTHOR]

Fungal pathogens must exhibit strong nutritional plasticity, effectively sensing and utilizing diverse nutrients to support virulence. How the signals generated by nutritional sensing are efficiently translated to the morphogenetic machinery for optimal growth and support of virulence remains incompletely understood. Here, we show that the conserved morphogenesis-related kinase, CotA, imparts isoform-specific control over Aspergillus fumigatus invasive growth in host-mimicking environments and during infection. CotA-mediated invasive growth is responsive to exogenous carbon source quality, with only preferred carbon sources supporting hyphal morphogenesis in a mutant lacking one of two identified protein isoforms. Strikingly, we find that the CotA protein does not regulate, nor is cotA gene expression regulated by, the carbon catabolite repression system. Instead, we show that CotA partially mediates invasive growth in specific carbon sources and virulence through the conserved downstream effector and translational repressor, SsdA. Therefore, A. fumigatus CotA accomplishes its conserved morphogenetic functions to drive pathogenic growth by translating host-relevant carbon source quality signals into morphogenetic outputs for efficient tissue invasive growth. Here, Martin-Vicente et al. show that the Aspergillus fumigatus protein kinase, CotA, controls invasive growth in an isoform dependent manner in response to carbon source diversity, partially mediated by the downstream effector, SsdA. [ABSTRACT FROM AUTHOR]

Grasses form morphologically derived, four-celled stomata, where two dumbbell-shaped guard cells (GCs) are flanked by two lateral subsidiary cells (SCs). This innovative form enables rapid opening and closing kinetics and efficient plant-atmosphere gas exchange. The mobile bHLH transcription factor MUTE is required for SC formation in grasses. Yet whether and how MUTE also regulates GC development and whether MUTE mobility is required for SC recruitment is unclear. Here, we transgenically impaired BdMUTE mobility from GC to SC precursors in the emerging model grass Brachypodium distachyon. Our data indicate that reduced BdMUTE mobility severely affected the spatiotemporal coordination of GC and SC development. Furthermore, although BdMUTE has a cell-autonomous role in GC division orientation, complete dumbbell morphogenesis of GCs required SC recruitment. Finally, leaf-level gas exchange measurements showed that dosage-dependent complementation of the four-celled grass morphology was mirrored in a gradual physiological complementation of stomatal kinetics. Together, our work revealed a dual role of grass MUTE in regulating GC division orientation and SC recruitment, which in turn is required forGCmorphogenesis and the rapid kinetics of grass stomata. [ABSTRACT FROM AUTHOR]

Tissue morphogenesis remains poorly understood. In plants, a central problem is how the 3D cellular architecture of a developing organ contributes to its final shape. We address this question through a comparative analysis of ovule morphogenesis, taking advantage of the diversity in ovule shape across angiosperms. Here, we provide a 3D digital atlas of Cardamine hirsuta ovule development at single cell resolution and compare it with an equivalent atlas of Arabidopsis thaliana. We introduce nerve-based topological analysis as a tool for unbiased detection of differences in cellular architectures and corroborate identified topological differences between two homologous tissues by comparative morphometrics and visual inspection. We find that differences in topology, cell volume variation and tissue growth patterns in the sheet-like integuments and the bulbous chalaza are associated with differences in ovule curvature. In contrast, the radialized conical ovule primordia and nucelli exhibit similar shapes, despite differences in internal cellular topology and tissue growth patterns. Our results support the notion that the structural organization of a tissue is associated with its susceptibility to shape changes during evolutionary shifts in 3D cellular architecture. [ABSTRACT FROM AUTHOR]

Tissue morphogenesis is intimately linked to the changes in shape and organisation of individual cells. In curved epithelia, cells can intercalate along their own apicobasal axes, adopting a shape named 'scutoid' that allows energy minimization in the tissue. Although several geometric and biophysical factors have been associated with this 3D reorganisation, the dynamic changes underlying scutoid formation in 3D epithelial packing remain poorly understood. Here, we use live imaging of the sea star embryo coupled with deep learningbased segmentation to dissect the relative contributions of cell density, tissue compaction and cell proliferation on epithelial architecture. We find that tissue compaction, which naturally occurs in the embryo, is necessary for the appearance of scutoids. Physical compression experiments identify cell density as the factor promoting scutoid formation at a global level. Finally, the comparison of the developing embryo with computational models indicates that the increase in the proportion of scutoids is directly associated with cell divisions. Our results suggest that apico-basal intercalations appearing immediately after mitosis may help accommodate the new cells within the tissue. We propose that proliferation in a compact epithelium induces 3D cell rearrangements during development. [ABSTRACT FROM AUTHOR]

Clarifying the mechanisms underlying shape alterations during insect metamorphosis is important for understanding exoskeletal morphogenesis. The large horn of the Japanese rhinoceros beetle Trypoxylus dichotomus is the result of drastic metamorphosis, wherein it appears as a rounded shape during pupation and then undergoes remodeling into an angular adult shape. However, the mechanical mechanismsunderlying this remodeling process remain unknown. In this study, we investigated the remodeling mechanisms of the Japanese rhinoceros beetle horn by developing a physical simulation. We identified three factors contributing to remodeling by biological experiments - ventral adhesion, uneven shrinkage, and volume reduction - which were demonstrated to be crucial for transformation using a physical simulation. Furthermore, we corroborated our findings by applying the simulation to the mandibular remodeling of stag beetles. These results indicated that physical simulation applies to pupal remodeling in other beetles, and the morphogenic mechanism could explain various exoskeletal shapes. [ABSTRACT FROM AUTHOR]

The development of fetal organs can be impacted by systemic changes in maternal circulation, with the placenta playing a pivotal role in maintaining pregnancy homeostasis and nutrient exchange. In clinical obstetrics, oxytocin (OXT) is commonly used to induce labor. To explore the potential role of OXT in the placental homeostasis of OXT, we compared OXT levels in neonatal cord blood among neonates (23–42 weeks gestation) whose mothers either received prenatal OXT or experienced spontaneous labor. Our previous research revealed that the oxytocin receptor (OXTR), essential in forming the blood–retina barrier, is expressed in the retinal pigment epithelium (RPE). We hypothesized that perinatal OXT administration might influence the development of the neural retina and its vasculature, offering therapeutic potential for retinal diseases such as retinopathy of prematurity (ROP). Plasma OXT levels were measured using a commercial OXT ELISA kit. Human fetal RPE (hfRPE) cells treated with OXT (10 µM) were assessed for gene expression via RNA sequencing, revealing 14 downregulated and 32 upregulated genes. To validate these differentially expressed genes (DEGs), hfRPE cells were exposed to OXT (0.01, 0.1, 1, or 10 µM) for 12 h, followed by RNA analysis via real-time PCR. Functional, enrichment, and network analyses (Gene Ontology term, FunRich, Cytoscape) were performed to predict the affected pathways. This translational study suggests that OXT likely crosses the placenta, altering fetal OXT concentrations. RNA sequencing identified 46 DEGs involved in vital metabolic and signaling pathways and critical cellular components. Our results indicate that the perinatal administration of OXT may affect neural retina and retinal vessel development, making OXT a potential therapeutic option for developmental eye diseases, including ROP. [ABSTRACT FROM AUTHOR]

PKD2 was first identified as the pathogenic protein for autosomal dominant polycystic kidney disease (ADPKD) and is widely recognized as an ion channel. Subsequent studies have shown that PKD2 is widely expressed in various animal tissues and plays a crucial role in tissue and organ development. Additionally, PKD2 is conserved from single-celled organisms to vertebrates. Here, we provide an overview of recent advances in the function of PKD2 in key model animals, focusing on the establishment of left–right organ asymmetry, renal homeostasis, cardiovascular development, and signal transduction in reproduction and mating. We specifically focus on the roles of PKD2 in development and highlight future prospects for PKD2 research. [ABSTRACT FROM AUTHOR]

Mastitis is a common disease worldwide that affects the development of the dairy industry due to its high incidence and complex etiology. Precise regulation of cell death and survival plays a critical role in maintaining internal homeostasis, organ development, and immune function in organisms, and regulatory abnormalities are a common mechanism of various pathological changes. Recent research has shown that regulated cell death (RCD) plays a crucial role in mastitis. The development of drugs to treat cell death and survival abnormalities that can be widely used in mastitis treatment has important clinical significance. This paper will review the molecular mechanisms of apoptosis, autophagy, pyroptosis, ferroptosis, and necroptosis and their regulatory roles in mastitis to provide a new perspective for the targeted treatment of mastitis. [ABSTRACT FROM AUTHOR]

SUMMARY: De novo shoot apical meristem (SAM) organogenesis during regeneration in tissue culture has been investigated for several decades, but the precise mechanisms governing early‐stage cell fate specification remain elusive. In contrast to SAM establishment during embryogenesis, in vitro SAM formation occurs without positional cues and is characterized by autonomous initiation of cellular patterning. Here, we report on the initial stages of SAM organogenesis and on the molecular mechanisms that orchestrate gene patterning to establish SAM homeostasis. We found that SAM organogenesis in tobacco calli starts with protuberance formation followed by the formation of an intact L1 layer covering the nascent protuberance. We also exposed a complex interdependent relationship between L1 and WUS expression and revealed that any disruption in this interplay compromises shoot formation. Silencing WUS in nascent protuberances prevented L1 formation and caused the disorganization of the outer cell layers exhibiting both anticlinal and periclinal divisions, suggesting WUS plays a critical role in the proper establishment and organization of L1 during SAM organogenesis. We further discovered that silencing TONNEAU1 prevents the exclusive occurrence of anticlinal divisions in the outermost layer of the protuberances and suppresses the acquisition of L1 cellular identity and L1 formation, ultimately impeding SAM formation and regeneration. This study provides a novel molecular framework for the characterization of a WUS/L1 interplay that mediates SAM formation during regeneration. Significance Statement: This study highlights the importance of establishing an intact L1 cell layer to promote de novo shoot apical meristem (SAM) organogenesis in vitro. It identifies a complex interdependence between WUS and ML1 expression in directing anticlinal divisions for L1 formation, which in turn initiates gene expression patterning in the SAM and its formation. Disrupting this WUS/L1 interplay impairs SAM regeneration, underscoring its central role. [ABSTRACT FROM AUTHOR]

SUMMARY: Petal size is determined by cell division and cell expansion. Jasmonic acid (JA) has been reported to be associated with floral development, but its regulatory mechanism affecting petal size remains unclear. Here, we reveal the vital role of JA in regulating petal size and the duration of the cell division phase via the key JA signaling component RhMYC2. We show that RhMYC2 expression is induced by exogenous treatment with methyl jasmonate and decreases from stage 0 to stage 2 of flower organ development, corresponding to the cell division phase. Furthermore, silencing RhMYC2 shortened the duration of the cell division phase, ultimately accelerating flowering opening and resulting in smaller petals. In addition, we determined that RhMYC2 controls cytokinin homeostasis in rose petals by directly activating the expression of the cytokinin biosynthetic gene LONELY GUY3 (RhLOG3) and repressing that of the cytokinin catabolism gene CYTOKININ OXIDASE/DEHYDROGENASE6 (RhCKX6). Silencing RhLOG3 shortened the duration of the cell division period and produced smaller petals, similar to RhMYC2 silencing. Our results underscore the synergistic effects of JA and cytokinin in regulating floral development, especially for petal size in roses. [ABSTRACT FROM AUTHOR]

Background: Cryptolaemus montrouzieri (Coccinellidae) is widely utilized as biological control agents in modern agriculture. A comprehensive understanding of its food preference can help guide mass rearing and safety management during field application of pest control. Although some studies have paid attentions to the impacts of prey shift on C. montrouzieri, little is known regarding the role of post-transcriptional regulations in its acclimation to unnatural preys. Results: We performed a genome-wide investigation on alternative splicing dynamics in C. montrouzieri in response to the predation transition from natural prey to unnatural ones. When feeding on undesired diets, 402–764 genes were differentially alternative spliced in C. montrouzieri. It is noteworthy that the majority of these genes (> 87%) were not differentially expressed, and these differentially spliced genes regulated distinct biological processes from differentially expressed genes, such as organ development and morphogenesis, locomotory behavior, and homeostasis processes. These suggested the functionally nonredendant role of alternative splicing in modulating physiological and metabolic responses of C. montrouzieri to the shift to undesired preys. In addition, the individuals feeding on aphids were subject to a lower level of changes in splicing than other alternative diets, which might be because of the similar chemical and microbial compositions. Our study further suggested a putative coupling of alternative splicing and nonsense-mediated decay (AS-NMD), which may play an important role in fine-tuning the protein repertoire of C. montrouzieri, and promoting its acclimation to predation changes. Conclusion: These findings highlight the key role of alternative splicing in modulating the acclimation of ladybirds to prey shift and provide new genetic clues for the future application of ladybirds in biocontrol. [ABSTRACT FROM AUTHOR]

A tight regulation of morphogen production is key for morphogen gradient formation and thereby for reproducible and organised organ development. Although many genetic interactions involved in the establishment of morphogen production domains are known, the biophysical mechanisms of morphogen source formation are poorly understood. Here we addressed this by focusing on the morphogen Sonic hedgehog (Shh) in the vertebrate neural tube. Shh is produced by the adjacently located notochord and by the floor plate of the neural tube. Using a data-constrained computational screen, we identified different possible mechanisms by which floor plate formation can occur, only one of which is consistent with experimental data. In this mechanism, the floor plate is established rapidly in response to Shh from the notochord and the dynamics of regulatory interactions within the neural tube. In this process, uniform activators and Shh-dependent repressors are key for establishing the floor plate size. Subsequently, the floor plate becomes insensitive to Shh and increases in size due to tissue growth, leading to scaling of the floor plate with neural tube size. In turn, this results in scaling of the Shh amplitude with tissue growth. Thus, this mechanism ensures a separation of time scales in floor plate formation, so that the floor plate domain becomes growth-dependent after an initial rapid establishment phase. Our study raises the possibility that the time scale separation between specification and growth might be a common strategy for scaling the morphogen gradient amplitude in growing organs. The model that we developed provides a new opportunity for quantitative studies of morphogen source formation in growing tissues. Author summary: As organs grow during development, molecules called morphogens instruct cells to adopt specific fates at the right place and time. Morphogens are produced in specialized source regions and spread through organs, forming gradients of concentration. How morphogen source regions form in growing organs and contribute to the establishment of morphogen gradients is poorly understood. In this study, we combine theory and experiments to investigate the formation of a key morphogen source in the developing mouse spinal cord called floor plate. Uncommitted spinal cord cells adopt floor plate identity in response to the morphogen Sonic hedgehog (Shh), which is produced by the adjacent notochord and by the floor plate cells themselves. Over time, the floor plate expands, producing more Shh. We found that in theory, the floor plate could expand by distinct mechanisms. In one scenario, Shh produced by the floor plate itself is used to convert more cells into floor plate. Alternatively, once a few cells are initially specified, the floor plate expands passively by tissue growth. Our experimental and theoretical analysis indicate that the latter scenario is the one that is relevant to the biological system. Similar temporal decoupling of specification and growth might occur in other growing organs. [ABSTRACT FROM AUTHOR]

The terminal cells of the Drosophila larval tracheal system are perhaps the simplest delivery networks, providing an analogue for mammalian vascular growth and function in a system with many fewer components. These cells are a prime example of single-cell morphogenesis, branching significantly over time to adapt to the needs of the growing tissue they supply. While the genetic mechanisms governing local branching decisions have been studied extensively, an understanding of the emergence of a global network architecture is still lacking. Mapping out the full network architecture of populations of terminal cells at different developmental times of Drosophila larvae, we find that cell growth follows scaling laws relating the total edge length, supply area, and branch density. Using time-lapse imaging of individual terminal cells, we identify that the cells grow in three ways: by extending branches, by the side budding of new branches, and by internally growing existing branches. A generative model based on these modes of growth recapitulates statistical properties of the terminal cell network data. These results suggest that the scaling laws arise from the coupled contributions of branching and internal growth. This study establishes the terminal cell as a uniquely tractable model system for further studies of transportation and distribution networks. [ABSTRACT FROM AUTHOR]

Perionyx excavatus, an indigenous earthworm possesses exceptional regeneration capacity. Their anterior regeneration features wound closure, regeneration induction and morphogenesis of damaged organs. This study involved a complete analysis of their transcriptomic dataset, with an emphasis on identifying the genes expressed during regeneration and predicting their implications in the process of regeneration and morphogenesis. Control (first ten segments) and test (5th day blastema) RNA samples of biological replicates were isolated and sequenced on NovaSeq. 6000 using PE150 read length. An average of 98.64% of high-quality data was retained with assembly showing better continuity with the average transcript length with 823 bp and N50 value of 1,858 bp. This is the first report on the comparative transcriptome of P. excavatus during anterior regeneration and this study will shed light on the complexity of annelid regeneration. [ABSTRACT FROM AUTHOR]

The cortical cytoskeleton of subpellicular microtubules (SPMTs) supports the Plasmodium ookinete morphogenesis during mosquito transmission of malaria. SPMTs are hypothesized to function as the cytoskeletal tracks in motor-driven cargo transport for apical organelle and structure assembly in ookinetes. However, the SPMT-based transport motor has not been identified in the Plasmodium. The cytoplasmic dynein is the motor moving towards the minus end of microtubules (MTs) and likely be responsible for cargo transport to the apical part in ookinetes. Here we screen 7 putative dynein heavy chain (DHC) proteins in the P. yoelii and identify DHC3 showing peripheral localization in ookinetes. DHC3 is localized at SPMTs throughout ookinete morphogenesis. We also identify five other dynein subunits localizing at SPMTs. DHC3 disruption impairs ookinete development, shape, and gliding, leading to failure in mosquito infection of Plasmodium. The DHC3-deficient ookinetes display defective formation or localization of apical organelles and structures. Rab11A and Rab11B interact with DHC3 at SPMTs in a DHC3-dependent manner, likely functioning as the receptors for the cargoes driven by SPMT-dynein. Disturbing Rab11A or Rab11B phenocopies DHC3 deficiency in ookinete morphogenesis. Our study reveals an SPMT-based dynein motor driving the transport of Rab11A- and Rab11B-labeled cargoes in the ookinete morphogenesis of Plasmodium. Liu et al. identify a subpellicular microtubule-based dynein motor in ookinetes of Plasmodium. This motor transports the cargos for apical organelle and structure assembly in ookinetes. Dynein-deficient parasites fail ookinete morphogenesis and mosquito transmission of Plasmodium. [ABSTRACT FROM AUTHOR]

Background: Phosphatidylinositol 3-kinase (PI3K) regulates cellular development and energy homeostasis. However, the roles of its subunits in organ development remain largely unknown. Methods: We explored the roles of PI3K catalytic subunits in steroidogenic factor 1 (SF1)-expressing cells through knockout (KO) of the p110α and p110β subunits. Results: We examined mice with a double KO of p110α and p110β in SF1-expressing cells (p110αβ KOSF1). Although these animals exhibited no significant changes in the development of the ventromedial hypothalamus, we noted pronounced hypotrophy in the adrenal cortex, testis, and ovary. Additionally, corticosterone and aldosterone levels were significantly reduced. The absence of these subunits also resulted in decreased body weight and survival rate, along with impaired glucose homeostasis, in p110αβ KOSF1 mice. Conclusion: The data demonstrate the specific roles of PI3K catalytic subunits in the development and function of SF1-expressing organs. [ABSTRACT FROM AUTHOR]

Models for fluid deformable surfaces provide valid theories to describe the dynamics of thin fluidic sheets of soft materials. To use such models in morphogenesis and development requires to incorporate active forces. We consider active geometric forces that respond to mean curvature gradients. Due to these forces, perturbations in shape can induce tangential flows, which can enhance the perturbation leading to shape instabilities. We numerically explore these shape instabilities and analyze the resulting dynamics of closed surfaces with constant enclosed volume. The numerical approach considers surface finite elements and a semi-implicit time stepping scheme and shows convergence properties, similar to those proven to be optimal for Stokes flow on stationary surfaces. [ABSTRACT FROM AUTHOR]

Talaromyces marneffei is a thermally dimorphic fungus that can cause life-threatening systemic mycoses, particularly in immunocompromised individuals. Fungal homeobox transcription factors control various developmental processes, including the regulation of sexual reproduction, morphology, metabolism, and virulence. However, the function of homeobox proteins in T. marneffei has not been fully explored. Here, we searched the T. marneffei genome for the total homeobox transcription factors and predicted their biological relevance by performing gene expression analysis in different cell types, including conidia, mycelia, yeasts, and during phase transition. RfeB is selected for further computational analysis since (i) its transcripts were differentially expressed in different phases of T. marneffei, and (ii) this protein contains the highly conserved protein-protein interaction region (IR), which could be important for pathobiology and have therapeutic application. To assess the structure-function of the IR region, in silico alanine substitutions were performed at three-conserved IR residues (Asp276, Glu279, and Gln282) of RfeB, generating a triple RfeB mutated protein. Using 3D modeling and molecular dynamics simulations, we compared the protein complex formation of wild-type and mutated RfeB proteins with the putative partner candidate TmSwi5. Our results demonstrated that the mutated RfeB protein exhibited increased free binding energy, elevated protein compactness, and a reduced number of atomic contacts, suggesting disrupted protein stability and interaction. Notably, our model revealed that the IR residues primarily stabilized the RfeB binding sites located in the central region (CR). This computational approach for protein mutagenesis could provide a foundation for future experimental studies on the functional characterization of RfeB and other homeodomain-containing proteins in T. marneffei. [ABSTRACT FROM AUTHOR]