Search

Deuterostomes make a sudden appearance in the fossil record during the early Cambrian. Two bilaterian groups, the chordates and the vetulicolians, are of particular interest for understanding early deuterostome evolution, and the main objective of this review is to examine the Cambrian diversity of these two deuterostome groups. The subject is of particular interest because of the link to vertebrates, and because of the enigmatic nature of vetulicolians. Lagerstätten in China and elsewhere have dramatically improved our understanding of the range of variation in these ancient animals. Cephalochordate and vertebrate body plans are well established at least by Cambrian Series 2. Taken together, roughly a dozen chordate genera and fifteen vetulicolian genera document part of the explosive radiation of deuterostomes at the base of the Cambrian. The advent of deuterostomes near the Cambrian boundary involved both a reversal of gut polarity and potentially a two-sided retinoic acid gradient, with a gradient discontinuity at the midpoint of the organism that is reflected in the sharp division of vetulicolians into anterior and posterior sections. A new vetulicolian (Shenzianyuloma yunnanense nov. gen. nov. sp.) with a laterally flattened, polygonal anterior section provides significant new data regarding vetulicolians. Its unsegmented posterior region (‘tail’) bears a notochord and a gut trace with diverticula, both surrounded by myotome cones.

Tissues in developing embryos exhibit complex and dynamic rearrangements that shape forming organs, limbs, and body axes. Directed migration, mediolateral intercalation, lumen formation, and other rearrangements influence the topology and topography of developing tissues. These collective cell behaviors are distinct phenomena but all involve the fine-grained control of cell polarity. Here we review recent findings in the dynamics of polarized cell behavior in both the Drosophila ovarian border cells and the Ciona notochord. These studies reveal the remarkable reorganization of cell polarity during organ formation and underscore conserved mechanisms of developmental cell polarity including the Par/atypical protein kinase C (aPKC) and planar cell polarity pathways. These two very different model systems demonstrate important commonalities but also key differences in how cell polarity is controlled in tissue morphogenesis. Together, these systems raise important, broader questions on how the developmental control of cell polarity contributes to morphogenesis of diverse tissues across the metazoa.

The vertebral column is a key component of the jawed vertebrate (gnathostome) body plan, but the primitive embryonic origin of this skeleton remains unclear. In tetrapods, all vertebral components (neural arches, haemal arches and centra) derive from paraxial mesoderm (somites). However, in teleost fishes, vertebrae have a dual embryonic origin, with arches derived from somites, but centra formed, in part, by secretion of bone matrix from the notochord. Here, we test the embryonic origin of the vertebral skeleton in a cartilaginous fish (the skate, Leucoraja erinacea) which serves as an outgroup to tetrapods and teleosts. We demonstrate, by cell lineage tracing, that both arches and centra are somite-derived. We find no evidence of cellular or matrix contribution from the notochord to the skate vertebral skeleton. These findings indicate that the earliest gnathostome vertebral skeleton was exclusively of somitic origin, with a notochord contribution arising secondarily in teleosts. [ABSTRACT FROM AUTHOR]

We present the development of the notochord of the Atlantic salmon ( Salmo salar L.), from early embryo to sexually mature fish. Over the salmon's lifespan, profound morphological changes occur. Cells and gross structures of the notochord reorganize twice. In the embryo, the volume of the notochord is dominated by large, vacuolated chordocytes; each cell can be modeled as a hydrostat organized into a larger cellular-hydrostat network, structurally bound together with desmosomes. After the embryo hatches and grows into a fry, vacuolated chordocytes disappear, replaced by extracellular lacunae. The formation of mineralized, segmental chordacentra stiffens the notochord and creates intervertebral joints, where tissue strain during lateral bending is now focused. As development proceeds towards the parr stage, a process of devacuolization and intracellular filament accumulation occur, forming highly dense, non-vacuolated chordocytes. As extracellular lacunae enlarge, they are enclosed by dense filamentous chordocytes that form transverse intervertebral septa, which are connected to the intervertebral ligaments, and a longitudinal notochordal strand. In the vertebral column of pelagic adults, large vacuolated chordocytes reappear; cells of this secondary population have a volume up to 19 000 times larger than the primary vacuolated chordocytes of the early notochord. In adults the lacunae have diminished in relative size. Hydrostatic pressure within the notochord increases significantly during growth, from 525 Pa in the alevins to 11 500 Pa in adults, at a rate of increase with total body length greater than that expected by static stress similarity. Pressure and morphometric measurements were combined to estimate the stress in the extracellular material of the notochordal sheath and intervertebral ligaments and the flexural stiffness of the axial skeleton. The functional significance of the morphological changes in the axial skeleton is discussed in relation to the different developmental stages and locomotor behavior changes over the lifespan of the fish. [ABSTRACT FROM AUTHOR]

The notochord is amidline structure common to all chordate animals; it provides mechanical and signaling cues for the developing embryo. In vertebrates, the notochord plays key functions during embryogenesis, being a source of developmental signals that pattern the surrounding tissues. It is composed of a core of vacuolated cells surrounded by an epithelial-like sheath of cells that secrete a thick peri-notochordal basement membrane made of different extracellular matrix (ECM) proteins. The correct deposition and organization of the ECM is essential for proper notochord morphogenesis and function. Work carried out in the past two decades has allowed researchers to dissect the contribution of different ECM components to this embryonic tissue. Here, we will provide an overview of these genetic and mechanistic studies. In particular, we highlight the specific functions of distinct matrix molecules in regulating notochord development and notochordderived signals. Moreover, we also discuss the involvement of ECM synthesis and its remodeling in the pathogenesis of chordoma, a malignant bone cancer that originates from remnants of notochord remaining after embryogenesis. [ABSTRACT FROM AUTHOR]

Spondylometaphyseal dysplasia Kozlowski type (SMDK) is a monogenic disorder within the TRPV4 dysplasia spectrum and has characteristic spinal and metaphyseal changes. We report skeletal MR imaging in a two-year-old patient who manifested typical clinical and radiographic features of SMDK. The diagnosis was confirmed by molecular analysis which revealed a mutation NM_021625.4 :c.1781G > A - p.(Arg594His) in exon 11 of the TRPV4 gene. We have documented abnormalities in endochondral formation of the long and short tubular bones as well as round bones of the wrists and feet. The vertebral bodies had increased thickness of hyaline cartilage which enveloped ossification centers. The vertebrae and discs also had abnormalities in size, shape and structure. These anomalies were most likely the consequence of notochordal remnants presence within the intervertebral discs and in the vertebral bodies. The advantages of MR imaging in bone dysplasias caused by TRPV4 mutations are emphasized in this article. [ABSTRACT FROM AUTHOR]

The notochord of the ascidian Ciona consists of only 40 cells, and is a longstanding model for studying organogenesis in a small, simple embryo. Here, we perform RNAseq on flow-sorted notochord cells from multiple stages to define a comprehensive Ciona notochord transcriptome. We identify 1364 genes with enriched expression and extensively validate the results by in situ hybridization. These genes are highly enriched for Gene Ontology terms related to the extracellular matrix, cell adhesion and cytoskeleton. Orthologs of 112 of the Ciona notochord genes have known notochord expression in vertebrates, more than twice as many as predicted by chance alone. This set of putative effector genes with notochord expression conserved from tunicates to vertebrates will be invaluable for testing hypotheses about notochord evolution. The full set of Ciona notochord genes provides a foundation for systemslevel studies of notochord gene regulation and morphogenesis. We find only modest overlap between this set of notochord-enriched transcripts and the genes upregulated by ectopic expression of the key notochord transcription factor Brachyury, indicating that Brachyury is not a notochord master regulator gene as strictly defined. [ABSTRACT FROM AUTHOR]

This study will examine how differences in measurements between bizygomatic and bigonial arches of the human face can provide relevant information regarding personality and abilities of the subject. Sample: 82 males. Group A: 55 subjects with the bizygomatic arch in contraction. Group B: 27 subjects without the bizygomatic arch in contraction. Subjects performed self-assessment tests in the following areas: ability incorporating themselves into the group, alexithymia and emotional expressiveness. Group A showed greater self-sufficiency and independence than group B, greater difficulty in describing and verbally expressing their emotions, less ability to express themselves emotionally through other forms of communication and reduced willingness to cooperate philanthropically. Results suggest a strong relationship between morphological structure of the bizygomatic arch and certain psychological characteristics. [ABSTRACT FROM AUTHOR]

Purpose: There is a paucity of research regarding both the development and the prevalence of the clival canal or clival foramen in fetuses. Reports that have examined child and adult populations have posited ideas for the development of the canal and foramen; however, they have done so in the absence of anatomical data from the fetal population. Therefore, the present study was performed to elucidate the development of the clival canal and foramen through the assessment of perinatal basioccipitals. Methods: This study analyzed 104 basioccipital bones, 60 from fetuses and 44 from newborns and infants. Dorsal surfaces of basioccipitals were assessed for the presence of anatomical variation with particular attention to the presence of clival canals and foramina. Among cases in which the presence of a clival canal or clival foramen was suspected, cannulation was performed for verification. Results: Of the 104 basioccipitals analyzed, 1 (0.96%) had a clival foramen. Clival canals were identified in seven basioccipitals (7:104; 6.73%), four of which were from fetuses. Trends in anatomical variations among basioccipitals were also identified and categorized. These categories were then evaluated relative to age in order to elucidate ontogeny. A model is presented to explain the development of the clival foramen, the clival canal, and the basioccipital, in general. Conclusions: The presence of a clival canal or foramen should be considered even among individuals of fetal age. The findings of this osteological study suggest that the clival canal and foramen develop around vascular structures and, therefore, signify vascular connections among nearby venous plexuses. [ABSTRACT FROM AUTHOR]

Introduction The apical ligament has long been reported to contain notochord remnants and thus might serve as a site of origin of chordoma formation at the skull base. However, to our knowledge, the histologic study of the apical ligament using histologic staining specific for notochordal tissue has not been previously performed. Therefore the current study was undertaken. Methods Fifteen apical ligament samples underwent histologic examination with specific markers for notochordal differentiation. Results Across all samples, there was no indication of any notochordal remnants. Conclusions On the basis of our cadaveric study, the apical ligament does not contain notochord tissue and in adults should not be considered a remnant of this structure. Moreover, it is unlikely that the apical ligament gives rise to chordomas at the craniocervical junction under normal circumstances. [ABSTRACT FROM AUTHOR]

In this report we utilized zebrafish ( Danio rerio ) embryos in a phenotypical high-content screen (HCS) to identify novel leads in a cancer drug discovery program. We initially validated our HCS model using the flavin adenosine dinucleotide (FAD) containing endoplasmic reticulum (ER) enzyme, endoplasmic reticulum oxidoreductase (ERO1) inhibitor EN460. EN460 showed a dose response effect on the embryos with a dose of 10 μM being significantly lethal during early embryonic development. The HCS campaign which employed a small library identified a promising lead compound, a naphthyl-benzoic acid derivative coined compound 1 which had significant dosage and temporally dependent effects on notochord and muscle development in zebrafish embryos. Screening a 369 kinase member panel we show that compound 1 is a PIM3 kinase inhibitor (IC 50 = 4.078 μM) and surprisingly a DAPK1 kinase agonist/activator (EC 50 = 39.525 μM). To our knowledge this is the first example of a small molecule activating DAPK1 kinase. We provide a putative model for increased phosphate transfer in the ATP binding domain when compound 1 is virtually docked with DAPK1. Our data indicate that observable phenotypical changes can be used in future zebrafish screens to identify compounds acting via similar molecular signaling pathways. [ABSTRACT FROM AUTHOR]

Background Context: Degenerative disc disease (DDD) remains without an effective therapy and presents a costly burden to society.Purpose: Based upon prior reports concerning the effects of notochordal cell-conditioned medium (NCCM) on disc cells, we performed a proof of principle study to determine whether NCCM could reduce cytotoxic stress-induced apoptosis in human disc nucleus pulposus (NP) cells.Study Design/setting: This is an "in vitro" fundamental or basic science study.Methods: Nucleus pulpous cells derived from 15 patients undergoing spinal surgery were treated with interleukin (IL)-1β and Fas ligand or etoposide in the presence of NCCM. We determined pro- or antiapoptotic events using activated caspase assays and determined genomic regulation of apoptosis using polymerase chain reaction arrays validated using Western blotting methods. We interrogated cellular apoptotic regulation using JC-1 dye and flow cytometry and performed enzyme-linked immunosorbent assays to evaluate NP inflammatory cytokine secretion.Results: Notochordal cell-conditioned medium inhibits cytotoxic stress-induced caspase-9 and -3/7 activities and maintains the mitochondrial membrane potential in human NP cells, thereby suppressing the intrinsic apoptotic pathway. Gene expression analysis revealed the X-linked inhibitor of apoptosis protein as a key player responsible for evading etoposide-induced apoptosis in the presence of NCCM, and we verified these data using Western blotting. Enzyme-linked immunosorbent assay results revealed distinct differences in IL-6 and IL-8 secretions by NP cells in response to etoposide in the presence of NCCM.Conclusions: Here we demonstrate for the first time that NCCM reduces cytotoxic stress-induced apoptosis in human NP cells. Soluble factors present in NCCM could be harnessed for the development of novel therapeutics for the treatment of DDD. [ABSTRACT FROM AUTHOR]

A substantial amount of data has highlighted the crucial influence of Shh signalling on the generation of diverse classes of neurons and glial cells throughout the developing central nervous system. A critical step leading to this diversity is the establishment of distinct neural progenitor cell domains during the process of pattern formation. The forming spinal cord, in particular, has served as an excellent model to unravel how progenitor cells respond to Shh to produce the appropriate pattern. In recent years, considerable advances have been made in our understanding of important parameters that control the temporal and spatial interpretation of the morphogen signal at the level of Shh-receiving progenitor cells. Although less studied, the identity and position of Shh source cells also undergo significant changes over time, raising the question of how moving the Shh source contributes to cell diversification in response to the morphogen. Here, we focus on the dynamics of Shh-producing cells and discuss specific roles for these time-variant Shh sources with regard to the temporal events occurring in the receiving field. [ABSTRACT FROM AUTHOR]

Background: The T-box family transcription-factor gene, Brachyury, has two expression domains with discrete functions during animal embryogenesis. The primary domain, associated with the blastopore, is shared by most metazoans, while the secondary domain, involved in the notochord, is specific to chordates. In most animals, Brachyury is present in a single copy, but in cephalochordates, the most basal of the chordates, the gene is present in two copies, suggesting allotment of the two domains to each of the duplicates. Results: In order to clarify whether Brachyury duplication occurred in the common ancestor of chordates after which one of duplicates was lost in the urochordate and vertebrate lineages, we estimated phylogenetic relationships of Brachyury genes and examined the synteny of a Brachyury-containing genomic region of deuterostomes with decoded genomes. The monophyletic origin of tandemly arranged Brachyury genes of cephalochordates indicates that the tandem duplication occurred in the cephalochordate lineage, but not in the chordate ancestor. Conclusions: Our results thus suggest that, in the common ancestor of chordates, a single copy of Brachyury acquired two expression domains and that the duplication was not involved in the acquisition of the notochord. However, in relation to regulatory mechanisms, both possibilities--namely a single copy with two domains and two copies with different domains--should be considered in future studies of Brachyury. [ABSTRACT FROM AUTHOR]

MicroRNAs are essential in many cellular processes. The ability to detect microRNAs is important for understanding its function and biogenesis. This study is aimed at using a molecular beacon to detect miR-430 in developing zebrafish embryos as a proof of principle. miR-430 is crucial for the clearance of maternal mRNA during maternal zygotic transition in embryonic development. Despite its known function, the temporal and spatial expression of miR-430 remains unclear. We used various imaging techniques, including laser scanning confocal microscopy, spinning disk, and lightsheet microscopy, to study the localization of miR-430 and any developmental defects possibly caused by the molecular beacon. Our results show that miR-430 is expressed early in development and is localized in distinct cytoplasmic granules where its target mRNA can be detected. We also show that the designed molecular beacon can inhibit the function of miR-430 and cause developmental defect in the brain, notochord, heart, and kidney, depending on the delivery site within the embryo, suggesting that miR-430 plays a diverse role in embryonic morphogenesis. When compared with morpholino, molecular beacon is 2 orders of magnitude more potent in inhibiting miR-430. Thus, our results reveal that in addition to being used as a valuable tool for the detection of microRNAs in vivo, molecular beacons can also be employed to inhibit microRNAs in a specific manner. [ABSTRACT FROM AUTHOR]

Background Chordoma are malignant tumors of the axial skeleton, which arise from remnants of the notochord. The Notochord (chorda dorsalis) is an essential embryonic structure involved in the development of the nervous system and axial skeleton. Therefore, the notochord seems to be the most biologically relevant control tissue to study chordoma in molecular biology research. Nevertheless, up to now mainly different tissues but not the notochord have been used as control for chordoma, due to difficulty of isolating notochordal tissue. Here, we describe a fast and precise method of isolating notochordal cells. Methods Examination of human fetuses, with a gestation of 9, 11 and 13 weeks, using (immuno)histochemical methods was performed. To isolate pure notochord cells for further molecular biology investigation five flash frozen fetuses between 9 and 10 weeks of gestation were dissected by microtome slicing. Thereafter pure notochord cells for further molecular biology investigation where harvested by using laser capture microdissection (LCM). RNA was extracted from these samples and used in quantitative PCR. Results This study illustrates notochord of embryonic spines in three different stages of gestation (9–11–13 weeks). Immunohistochemical staining with brachyury showed strong staining of the notochord, but also weak staining of the intervertebral disc and vertebral body. LCM of notochord slices and subsequent total RNA extraction resulted in a good yield of total RNA. qPCR analysis of two housekeeping genes confirmed the quality of the RNA. Conclusion LCM is a fast and precise method to isolate notochord and the quality and yield RNA extracted from this tissue is sufficient for qPCR analysis. Therefore early embryo notochord isolated by LCM is suggested to be the gold standard for future research in chordoma development, classification and diagnosis. [ABSTRACT FROM AUTHOR]

The foxd1 gene (previously known as Brain Factor 2/BF2) is expressed during early Xenopus laevis development. At gastrula stages, foxd1 is expressed in dorsal mesoderm regions fated for muscle and notochord, while at neurula stages, foxd1 is expressed in the forebrain region. Previous studies in the neural plate showed that FoxD1 protein acts as transcriptional repressor downstream of BMP antagonism, neuralizing the embryo to control anterior neural cell fates. FoxD1 mesoderm function was not rigorously analyzed, but ectopic FoxD1 levels increased muscle marker expression in embryos. Using a FoxD1-specific antisense morpholino oligonucleotide, we knocked down endogenous FoxD1 protein activity in developing Xenopus embryos. In this present study, we show that FoxD1 is crucial for dorsal mesoderm formation. Analogous to neural tissue, FoxD1 acts downstream of BMP antagonism to induce dorsal mesoderm cell fates, such as muscle and notochord. FoxD1 is sensitive to its local signaling environment, having differential transcription factor activity in the presence or absence of Wnt or BMP signaling. FoxD1 induces posterior neural tissue in the presence of Wnt or BMP activities, but its activity is restricted to "normal" anterior neural tissue induction when BMP and Wnt activities are repressed. In dorsal mesoderm, FoxD1 interacts with Wnt signaling and BMP antagonism to induce muscle and notochord, while simultaneously repressing more anterior and ventral mesoderm cell fates. FoxD1 protein has multiple activities that are masked or released in the different germ layers as a function of the local signaling environment. [ABSTRACT FROM AUTHOR]

This is an analytical study which presents a rigorous biomechanical interpretation of the well known but poorly understood two-unit skull of extant Latimeria and extinct non-dipnoan sarcopterygian fishes. The two units, anterior ethmosphenoid and posterior otoccipital, are hinged, dorsally, by intracranial syndesmosis between parietal and postparietal bones of the skull roof, and interconnected, centrally, by intracranial segment of the notochord and, ventrally, by a very strong paired subcephalic muscle unique to these fishes. This muscle depresses the anterior unit with the upper jaw, and this movement is kinematically coupled, in Latimeria, with the mandible elevation and, in basal sarcopterygians, with narrowing of the jaws and the oropharyngeal cavity. However, the muscular antagonist able to raise the anterior unit was never found. Neither manipulations on thawed Latimeria nor modern techniques of CT scanning and computer modeling helped to solve the puzzle. To find the way out, researchers were forced to rely, implicitly, on various fantastic mechanisms, such as strut-like action of ligaments, positive mechanical work of elongating muscles, mechanical force action without opposite reaction and depression of the snout without elevation, etc. An accurate analysis of statics of the head of Latimeria shows that all of the most important muscles (m. subcephalicus, m. levator arcus palatini, m. coracomandibularis and m. adductor mandibulae) are synergists in respect of snout depression. I suggest a new idea that their antagonist, which is only possible, is parietal musculature acting via notochord. Indeed, the longitudinal contraction of the trunk myomeres causes some shortening of postcranial segment of the notochord, and consequently, forward protrusion of its liquid-filled intracranial segment. Thus, the last pushes, as a hydraulic drive, the anterior skull unit. The problem is posed, whether the cranial muscles depressing the snout are able to counteract the pressure force in the notochord produced by powerful parietal musculature during undulatory swimming of the fish. Otherwise, the skull mechanism could be broken. Calculation of physiological cross-sectional areas of major muscles involved allows to state that the m. subcephalicus is strong enough to counteract myomeric contraction. In basal sarcopterygians, the m. adductor mandibulae did not yet participate in this struggle because the hyomandibular suspension of the jaws was not shifted from the jaw joint onto the retroarticular process of the mandible. The biomechanic-based explanation is suggested of how this shift could occur gradually in the evolution of coelacanths. The second novelty of Latimeria and its relatives, the forward shift of the intracranial syndesmosis relative to the notochordal apex, is explained too, as a means to engage ligamentous suspension of the intracranial notochord under prootic bones in stopping the snout elevation under the pressure of the notochord. The new idea on adaptive significance of the neurocranial kinesis of sarcopterygian fishes is suggested: this mechanism allows the recruitment of powerful parietal musculature into prey suction with water by oropharyngeal expansion. [ABSTRACT FROM AUTHOR]

The head and anterior trunk region of most actinopterygian fishes is stiffened as, uniquely within vertebrates, the pectoral girdles have a direct and often strong connection through the posttemporal to the posterior region of the skull. Members of the mesopelagic fish family Stomiidae have their pectoral girdle separated from the skull. This connection is lost in several teleost groups, but the stomiids have an additional evolutionary novelty—a flexible connection between the occiput and the first vertebra, where only the notochord persists. Several studies suggested that stomiids engulf significantly large prey items and conjectured about the functional role of the anterior part of the vertebral column; however, there has been no precise anatomical description of this complex. Here we describe a unique configuration comprising the occiput and the notochordal sheath in Aristostomias, Eustomias, Malacosteus, Pachystomias, and Photostomias that represents a true functional head joint in teleosts and discuss its potential phylogenetic implications. In these genera, the chordal sheath is folded inward ventrally beneath its connection to the basioccipital and embraces the occipital condyle when in a resting position. In the resting position (wherein the head is not manipulatively elevated), this condyle is completely embraced by the ventral fold of the notochord. A manual manipulative elevation of the head in cleared and stained specimens unfolds the ventral sheath of the notochord. As a consequence, the cranium can be pulled up and back significantly farther than in all other teleost taxa that lack such a functional head joint and thereby can reach mouth gapes up to 120°. [ABSTRACT FROM AUTHOR]

Back pain caused by intervertebral disc (IVD) degeneration has a major socio-economic impact in humans, yet historically has received minimal attention in species other than humans, mice and dogs. However, a general growing interest in this unique organ prompted the expansion of IVD research in rats, rabbits, cats, horses, monkeys, and cows, further illuminating the complex nature of the organ in both healthy and degenerative states. Application of recent biotechnological advancements, including single cell RNA sequencing and complex data analysis methods has begun to explain the shifting inflammatory signaling, variation in cellular subpopulations, differential gene expression, mechanical loading, and metabolic stresses which contribute to age and stress related degeneration of the IVD. This increase in IVD research across species introduces a need for chronicling IVD advancements and tissue biomarkers both within and between species. Here we provide a comprehensive review of recent single cell RNA sequencing data alongside existing case reports and histo/morphological data to highlight the cellular complexity and metabolic challenges of this unique organ that is of structural importance for all vertebrates.

In the course of SRY-box transcription factor 6 (SOX6) expression profiling in human embryonic tissue, SOX 6 was found to be highly expressed in the notochord, based on the findings of immunohistochemistry (IHC). Sox6 is also expressed in the neural tube and the distribution of SOX6 is located in the ventral and dorsal zones of the neural tube. In contrast to the findings that SOX6-positive cells were located on the floor plate of the neural tube, OLIG2- and NKX2.2-expressing cells were lacking on the floor plate of the neural tube, and their expression was restricted only to the ventral zone of the neural tube. The expression patterns of SOX9 were similar to those of OLIG2 and NKX2.2 in the neural tube. NKX2.2 and OLIG2 are not expressed in the notochord, but SOX9 and SOX6 are. Because Sox6 is highly expressed in the notochord, the present study investigated whether or not SOX6 is an immunohistochemical marker for the pathologic diagnosis of chordoma, a neoplasm derived from the notochord. IHC revealed that chordoma was strongly positive for SOX6 in two cases of chordoma, one of which occurred in the sacrococcygeal region and another that developed at the base of the skull, suggesting that SOX6 is a useful marker for the histopathologic diagnosis of chordoma., Competing Interests: VThe author declares that there are no conflicts of interest., (2023 The Japan Society of Histochemistry and Cytochemistry.)

The control of cell numbers and the establishment of cell types are two processes that are essential in early embryonic development. We have a reasonable understanding of how these processes occur individually, but we have considerably less sophisticated understanding of how these processes are linked. Tunicates have fixed cell lineages with predictable cell cycles, making them well suited to investigate these processes. In the ascidian Ciona, we show that the transcription factor Zic-r.b, known to be involved in establishing several cell types in early development also activates the expression of the cell cycle inhibitor CDKN1B. Zic-r.b is a major missing component of the cell division clock establishing specific cell numbers. We also show that a larvacean homolog of Zic-r.b is expressed one cell cycle earlier than its Ciona counterpart. The early expression in larvaceans may explain why they have half as many notochord cells as ascidians and may illustrate a general mechanism to evolve changes in morphology., (Copyright © 2023. Published by Elsevier Inc.)

The effect of mechanical extension on the differentiation of axial mesoderm in double explants (sandwiches) of Xenopus laevis embryonic tissues isolated during the early gastrula-late neurula developmen-tal period is studied. In explants at the early gastrula stage, artificial extension orients and stimulates isolated differentiation of the notochord and somites as well as their joint formation. Moreover, extension facilitated the formation of the normal anatomical structure of the notochord and affected expression of Chordin gene. At the late gastrula stage, the effect of artificial extension on joint somite-notochord differentiation was weaker. At the stage of late neurula, somites were sometimes formed in explants lacking a notochord anlage. Thus, at earlier stages, the formation of somites was stimulated by contacts with the notochord and joint development of both structures was mechanical dependent, while at the later stages, somites developed inde-pendently of the notochord. Thus, the role of tissue extension is primarily the establishment of normal mor-phology and expression of Chordin was located in the direction of extension. [ABSTRACT FROM AUTHOR]

Caudal regression syndrome (CRS) is a rare congenital disorder characterized by developmental abnormalities of caudal spinal segments. To date, the etiology of CRS is unclear; sporadic cases are strongly associated with maternal diabetes, while familiar recurrence is infrequent. We describe in detail the prenatal clinical and sonographic findings of a recently described hereditary caudal regression syndrome, in four fetuses reported to be homozygous for a mutation in the T (brachyury) gene. The syndrome occurred in three consanguineous, but unrelated families, originating from the same geographical area. All affected fetuses had persistence of the notochord in association with abnormal vertebral ossification, sacral agenesis, and bilateral clubfoot. These findings suggest that, in case of prenatal diagnosis of sacral agenesis, an advanced ultrasound examination should assess the vertebral ossification and the rare persistence of the notochord, in order to rule the involvement of the T gene. [ABSTRACT FROM AUTHOR]

Study Design: In vitro cell culture model. Purpose: To investigate the effects of RNA interference (RNAi) on p75 expression and viability of rat notochordal cells treated with serum deprivation. Overview of Literature: RNAi enables the inhibition of specific genes by sequence-specific gene silencing using a double-stranded RNA. Methods: Notochordal cells were isolated, cultured, and placed in 10% (control) or 0% (apoptosis-promoting) fetal bovine serum (FBS) for 48 hours. The expression of p75, apoptosis, and cell proliferation were determined. To suppress p75 expression, a small interfering RNA (siRNA) was synthesized against p75 (p75 siRNA) and transfected into cells. The suppression of p75 mRNA expression was investigated using the reverse transcription-polymerase chain reaction. The degree of p75 suppression was semiquantitatively analyzed using densitometry. The effect of p75 siRNA on apoptosis and proliferation of cells was determined. Solutions of an unrelated siRNA and transfection agent alone served as controls. Results: Serum deprivation significantly increased apoptosis by 40.3%, decreased proliferation of notochordal cells by 45.3% (both, p <0.001), and upregulated p75 expression. The p75 siRNA suppressed p75 expression in cells cultured in 0% FBS. The rate of suppression by p75 siRNA of p75 mRNA was 72.9% (p <0.001). Suppression of p75 expression by p75 siRNA inhibited apoptosis by 7% and increased proliferation by 14% in cells cultured in 0% FBS (both, p <0.05). Conclusions: siRNA-mediated suppression of p75 inhibited apoptosis and increased proliferation of notochordal cells under conditions of serum deprivation, suggesting that RNAi might serve as a novel therapeutic approach for disc degeneration caused by insufficient viability of disc cells through the suppression of the expression of harmful genes. [ABSTRACT FROM AUTHOR]

The reporting of the outcomes of flap reconstruction is often based on numerical success rates. Whilst this remains a useful variable with which to measure success, it is limited in its ability to reflect the complex processes involved. The lack of consistency in the categorisation of outcomes of flap reconstruction in the head and neck could potentially lead us to lose the opportunity to fully capture the implications of its success or failure, or both. We propose a classification that moves away from primarily reporting the results of its binary nature, and focuses more on the process of reconstruction, particularly in the head and neck. [ABSTRACT FROM AUTHOR]

esculetin, a natural coumarin, has anti-osteoclastic activity on cell line. We studied the effect of esculetin in vivo. Zebra fish larvae were raised in water containing various concentrations of esculetin. The area and intensity of ossified notochord was measured. Toxicity study of esculetin on adult zebra fish was performed. The caudal fin of zebrafish was amputated and the fishes were exposed to various concentrations of esculetin. Area of the regenerated fin was found to be measured. The intensity of mineralization of zebra fish larvae was significantly more with 10μg/mL esculetin. esculetin was safe upto 100mg/L. The area of the regenerated fin was not statistically significant amongst the different groups. esculetin showed significant increased osteogenesis in zebrafish larvae. Further investigation is needed as the study has certain innate limitations. [ABSTRACT FROM AUTHOR]

Diastematomyelia is a rare dysraphic lesion of spinal cord and the defect occurs as a result of an incorrect development of notochord between 15th and 18th day of pregnancy. In this defect, the spinal cord splits into two hemicords in sagittal plane. We hereby present a case of 30 years old female who had been experiencing spine pain without any neurological deficit for over 10 years. Despite the confirmed osseous anomalies of the lumbar spine, the correct diagnosis was established only after performing the MRI. She was treated surgically and was asked to come for regular neurological examinations after discharge.