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The formation of embryonic axes is a critical step during animal development, which contributes to establishing the basic body plan in each particular organism. Wnt signaling pathways play pivotal roles in this fundamental process. Canonical Wnt signaling that is dependent on β-catenin regulates the patterning of dorsoventral, anteroposterior, and left–right axes. Non-canonical Wnt signaling that is independent of β-catenin modulates cytoskeletal organization to coordinate cell polarity changes and asymmetric cell movements. It is now well documented that components of these Wnt pathways biochemically and functionally interact to mediate cell–cell communications and instruct cellular polarization in breaking the embryonic symmetry. The dysfunction of Wnt signaling disrupts embryonic axis specification and proper tissue morphogenesis, and mutations of Wnt pathway genes are associated with birth defects in humans. This review discusses the regulatory roles of Wnt pathway components in embryonic axis formation by focusing on vertebrate models. It highlights current progress in decoding conserved mechanisms underlying the establishment of asymmetry along the three primary body axes. By providing an in-depth analysis of canonical and non-canonical pathways in regulating cell fates and cellular behaviors, this work offers insights into the intricate processes that contribute to setting up the basic body plan in vertebrate embryos. [ABSTRACT FROM AUTHOR]

Purpose: The tibial anatomical anteroposterior (AP) axis "Akagi's line" was originally defined on computed tomography (CT) in total knee arthroplasty (TKA); however, its intraoperative reproducibility remains unknown. This study aimed to evaluate the intraoperative reproducibility of the Akagi's line and its effect on postoperative clinical outcomes. Methods: This prospective study included 171 TKAs. The rotational angle of the intraoperative Akagi's line relative to the original Akagi's line (RAA) defined on CT was measured. The RAA was calculated based on the tibial component rotational angles relative to the intraoperative Akagi's line measured using the navigation system and CT. The effects of RAA on postoperative clinical outcomes and rotational alignments of components were also evaluated. Results: The mean absolute RAA (standard deviation) value was 5.5° (3.9°). The range of RAA was 22° internal rotation to 16° external rotation. Intraoperative Akagi's line outliers (RAA > 10°) were observed in 14% of the knees (24 knees). In outlier analysis, the tibial component rotation angle was externally rotated 6.5° (5.6°) in the outlier group and externally rotated 3.7° (4.2°) in the nonoutlier group (≤10°), with a significant difference between the two groups. Additionally, the outlier group (RAA > 10°) showed lower postoperative clinical outcomes. Conclusion: The original Akagi's line defined on CT showed insufficient reproducibility intraoperatively. The poor intraoperative detection of Akagi's line could be the reason for the tibial component rotational error and worse postoperative clinical outcomes. Level of Evidence: Level IV, case series. [ABSTRACT FROM AUTHOR]

Two new species of cornutan stylophora of the genus Phyllocystis are described from the Volkhov Regional Stage (Middle Ordovician, Dapingian) of Baltica. This indicates a biogeographic connection between the Afro-European part of Gondwana and Baltica since the very beginning of the Middle Ordovician. Both species were confined to cold-water, shallow basins with low water mobility. Analysis of the axial symmetry of stylophorans and the location of the hydropore indicates the absence of torsion in their ontogeny and the location of the ambulacral system to the right of their anteroposterior axis. To explain this morphology, two alternative hypotheses are proposed: (1) inversion in the development of right and left coeloms; (2) inverted state of stylophorans compared to other invertebrates, in which respect they resemble chordates in terms of the position of the dorsal and ventral sides. [ABSTRACT FROM AUTHOR]

Abstract Purpose The tibial anatomical anteroposterior (AP) axis “Akagi's line” was originally defined on computed tomography (CT) in total knee arthroplasty (TKA); however, its intraoperative reproducibility remains unknown. This study aimed to evaluate the intraoperative reproducibility of the Akagi's line and its effect on postoperative clinical outcomes. Methods This prospective study included 171 TKAs. The rotational angle of the intraoperative Akagi's line relative to the original Akagi's line (RAA) defined on CT was measured. The RAA was calculated based on the tibial component rotational angles relative to the intraoperative Akagi's line measured using the navigation system and CT. The effects of RAA on postoperative clinical outcomes and rotational alignments of components were also evaluated. Results The mean absolute RAA (standard deviation) value was 5.5° (3.9°). The range of RAA was 22° internal rotation to 16° external rotation. Intraoperative Akagi's line outliers (RAA > 10°) were observed in 14% of the knees (24 knees). In outlier analysis, the tibial component rotation angle was externally rotated 6.5° (5.6°) in the outlier group and externally rotated 3.7° (4.2°) in the nonoutlier group (≤10°), with a significant difference between the two groups. Additionally, the outlier group (RAA > 10°) showed lower postoperative clinical outcomes. Conclusion The original Akagi's line defined on CT showed insufficient reproducibility intraoperatively. The poor intraoperative detection of Akagi's line could be the reason for the tibial component rotational error and worse postoperative clinical outcomes. Level of Evidence Level IV, case series.

The formation of embryonic axes is a critical step during animal development, which contributes to establishing the basic body plan in each particular organism. Wnt signaling pathways play pivotal roles in this fundamental process. Canonical Wnt signaling that is dependent on β-catenin regulates the patterning of dorsoventral, anteroposterior, and left–right axes. Non-canonical Wnt signaling that is independent of β-catenin modulates cytoskeletal organization to coordinate cell polarity changes and asymmetric cell movements. It is now well documented that components of these Wnt pathways biochemically and functionally interact to mediate cell–cell communications and instruct cellular polarization in breaking the embryonic symmetry. The dysfunction of Wnt signaling disrupts embryonic axis specification and proper tissue morphogenesis, and mutations of Wnt pathway genes are associated with birth defects in humans. This review discusses the regulatory roles of Wnt pathway components in embryonic axis formation by focusing on vertebrate models. It highlights current progress in decoding conserved mechanisms underlying the establishment of asymmetry along the three primary body axes. By providing an in-depth analysis of canonical and non-canonical pathways in regulating cell fates and cellular behaviors, this work offers insights into the intricate processes that contribute to setting up the basic body plan in vertebrate embryos.

Each vertebrate species appears to have a unique timing mechanism for forming somites along the vertebral column, and the process in human remains poorly understood at the molecular level due to technical and ethical limitations. Here, we report the reconstitution of human segmentation clock by direct reprogramming. We first reprogrammed human urine epithelial cells to a presomitic mesoderm (PSM) state capable of long‐term self‐renewal and formation of somitoids with an anterior‐to‐posterior axis. By inserting the RNA reporter Pepper into HES7 and MESP2 loci of these iPSM cells, we show that both transcripts oscillate in the resulting somitoids at ~5 h/cycle. GFP‐tagged endogenous HES7 protein moves along the anterior‐to‐posterior axis during somitoid formation. The geo‐sequencing analysis further confirmed anterior‐to‐posterior polarity and revealed the localized expression of WNT, BMP, FGF, and RA signaling molecules and HOXA‐D family members. Our study demonstrates the direct reconstitution of human segmentation clock from somatic cells, which may allow future dissection of the mechanism and components of such a clock and aid regenerative medicine. Synopsis: Spatial patterning and temporal rhythmicity of gene expression define human embryogenesis during primitive streak stages but have been notoriously difficult to explore. This resource establishes a reprogramming culture system to mimic spatio‐temporal dynamics during somitogenesis and body axis formation, offering new insights into the signaling pathways involved. Direct reprogramming of human urine epithelial cells into presomitic mesoderm (PSM) cells recapitulates somitogenic differentiation and tissue segmentation.The Nodal pathway is required for urine‐induced PSM (UiPSM) self‐organization into somitoids and long‐term culture.UiPSM‐derived somitoids show oscillation of HES7 and MESP2 transcripts.UiPSM‐derived somitoids establish anterior–posterior polarity and regional expression of WNT, BMP, FGF, and RA signaling pathway components. [ABSTRACT FROM AUTHOR]

In insect embryos, anteroposterior patterning is coordinated by the sequential expression of the ‘timer’ genes caudal, Dichaete, and odd-paired, whose expression dynamics correlate with the mode of segmentation. In Drosophila, the timer genes are expressed broadly across much of the blastoderm, which segments simultaneously, but their expression is delayed in a small ‘tail’ region, just anterior to the hindgut, which segments during germband extension. Specification of the tail and the hindgut depends on the terminal gap gene tailless, but beyond this the regulation of the timer genes is poorly understood. We used a combination of multiplexed imaging, mutant analysis, and gene network modelling to resolve the regulation of the timer genes, identifying 11 new regulatory interactions and clarifying the mechanism of posterior terminal patterning. We propose that a dynamic Tailless expression gradient modulates the intrinsic dynamics of a timer gene cross-regulatory module, delineating the tail region and delaying its developmental maturation.

Minimal in vitro systems composed of embryonic stem cells (ESCs) have been shown to recapitulate the establishment of the anteroposterior (AP) axis. In contrast to the native embryo, ESC aggregates - such as gastruloids - can break symmetry, which is demarcated by polarization of the mesodermal marker T, autonomously without any localized external cues. However, associated earliest patterning events, such as the spatial restriction of cell fates and concomitant transcriptional changes, remain poorly understood. Here, we dissect the dynamics of AP axis establishment in mouse gastruloids, particularly before external Wnt stimulation. Through single-cell RNA sequencing, we identify key cell state transitions and the molecular signatures of T+ and T- populations underpinning AP polarization. We also show that this process is robust to modifications of aggregate size. Finally, transcriptomic comparison with the mouse embryo indicates that gastruloids develop similar mesendodermal cell types, despite initial differences in their primed pluripotent populations, which adopt a more mesenchymal state in lieu of an epiblast-like transcriptome. Hence, our findings suggest the possibility of alternate ESC states in vivo and in vitro that can converge onto similar cell fates., Competing Interests: Competing interests The authors declare no competing or financial interests., (© 2024. Published by The Company of Biologists Ltd.)

During recent decades, the study of anatomical anomalies has been of great relevance for research on development and its evolution. Yet most animal groups have never been studied under this perspective. In annelids, one of the most common and remarkable anomalies is anteroposterior axis bifurcation, that is animals that have two or more heads and/or tails. Bifurcated annelids were first described in the 18th century and have been occasionally reported since then. However, these animals have rarely been considered other than curiosities, one‐off anomalies, or monsters, and a condensed but comprehensive analysis of this phenomenon is lacking. Such an analysis of the existing knowledge is necessary for addressing the different patterns of annelid bifurcation, as well as to understand possible developmental mechanisms behind them and their evolution. In this review we summarize reports of annelid bifurcation published during the last 275 years and the wide variety of anatomies they present. Our survey reveals bifurcation as a widespread phenomenon found all over the annelid tree. Moreover, it also shows that bifurcations can be classified into different types according to anatomy (lateral versus dorsoventral) or developmental origin (embryonic versus postembryonic, the latter occurring in relation to regeneration, reproduction, or growth). Regarding embryos, three different types of bifurcation can be found: conjoined twins (in clitellates); Janus embryos (two posterior ends with a single head which shows duplicated structures); and duplicitas cruciata embryos (with anterior and posterior bifurcation with a 90° rotation). In adults, we show that while lateral bifurcation can result in well‐integrated phenotypes, dorsoventral bifurcation cannot since it requires the discontinuity of at least some internal organs. The relevance of this distinction is highlighted in the case of the Ribbon Clade, a group of syllid annelids in which some species reproduce by collateral and successive gemmiparity (which involves dorsoventral bifurcation), while others grow by branching laterally. Although most known cases of bifurcation came from accidental findings in the wild or were unintentionally produced, experimental studies resulting in the induction of bifurcation of both embryos and adults are also reviewed. In embryos, these experimental studies show how mechanical or chemical disruption of the zygote can result in bifurcation. In adults, the ventral nervous system and the digestive tract seem to play a role in the induction of bifurcation. Based on the reviewed evidence, we argue that the long‐forgotten study of annelid developmental anomalies should be incorporated into the growing field of annelid EvoDevo and examined with modern techniques and perspectives. [ABSTRACT FROM AUTHOR]

Purpose. To conduct a comparative analysis of the anatomical parameters of the eyeball in children with ametropia, congenital glaucoma, aphakia and artiphakia.Material and methods. The study involved 73 patients (146 eyes) aged 5 to 12 years with ametropia, congenital glaucoma, aphakia and artiphakia and was carried out on an ultrasonic device STRONG 6000 T in the A-scan mode with the 10 MHz sensor set for three points.Results. A significant increase in the size of axial length of the eyeball in moderate and high myopia and in the vertical size in high myopia were revealed. In high hyperopia, sagittal dimensions were reduced while the transverse dimensions were a bit greater than the sagittal ones. In far-advanced stage of congenital glaucoma, a significant increase in eyeball dimensions was noted both in the axial direction and in the transverse — horizontal direction. No significant differences in sagittal and transverse dimensions were noted in aphakia and artiphakia. Conclusion. For a comprehensive assessment of the clinical course of the disease, in particular as concerns the condition of the fibrous capsule of the eye in children with ametropia, congenital glaucoma, aphakia and artiphakia, echobiometric indicators characterizing sagittal and transverse (vertical and horizontal) sizes of the eyeball should be taken into account.

Tailless is a committed transcriptional repressor and principal regulator of the brain and eye development in Drosophila. Rpd3, the histone deacetylase, is an established repressor that interacts with co-repressors like Sin3a, Prospero, Brakeless and Atrophin. This study aims at deciphering the role of Rpd3 in embryonic segmentation and larval brain development in Drosophila. It delineates the mechanism of Tailless regulation by Rpd3, along with its interacting partners. There was a significant reduction in Tailless in Rpd3 heteroallelic mutant embryos, substantiating that Rpd3 is indispensable for the normal Tailless expression. The expression of the primary readout, Tailless was correlative to the expression of the neural cell adhesion molecule homologue, Fascilin2 (Fas2). Rpd3 also aids in the proper development of the mushroom body. Both Tailless and Fas2 expression are reported to be antagonistic to the epidermal growth factor receptor (EGFR) expression. The decrease in Tailless and Fas2 expression highlights that EGFR is upregulated in the larval mutants, hindering brain development. This study outlines the axis comprising Rpd3, dEGFR, Tailless and Fas2, which interact to fine-tune the early segmentation and larval brain development. Therefore, Rpd3 along with Tailless has immense significance in early embryogenesis and development of the larval brain.

Purpose: Although the tibial rotation axis is significant in knee arthroplasty, no reliable extraarticular landmark has been proposed. We hypothesized that the tibial lateral axis (TLA), a tangential line of the lateral tibial surface, is perpendicular to the surgical epicondylar axis (SEA) and compared it to other existing landmarks by 3D-CT. Methods: Fifty legs in 25 consecutive patients were studied. Using their preoperative CT, the TLAs were identified on slices at 10–50% of the total length of the tibia and the measured differences of angles against the line perpendicular to the SEA (the tibial AP axis) were calculated. The differences between the SEA and the femoral and tibial posterior condylar axis, Akagi's line and the line between the medial intercondylar spine and the medial border of the patellar tendon (sAP line)(intraarticular), the ankle axis, and the transmalleolar axis (extraarticular) were also calculated and compared. Results: The mean values of TLA at 10%, 20%, 30% were virtually parallel to the SEA (0.97° ± 4.84°, 0.02° ± 4.61°, 1.10° ± 4.97°, respectively). They were equivalent to existing intraarticular landmarks and superior to existing extraarticular landmarks, and these levels corresponded to the tip to the lower end of the tibial tubercle (at 10.8% and 17.0% of total tibial length). Conclusion: The proximal TLAs can be an extraarticular bony landmark that indicates the line perpendicular to the SEA. A prospective study is needed to prove the validity and accuracy of the axes clinically. [ABSTRACT FROM AUTHOR]

In vertebrates, vertebral primordia, called somites, are formed from the head to the tail along the anteroposterior axis of the body during development. The presomitic mesoderm (PSM), which differentiates into somites, is formed by continuous supply of new cells derived from the caudal lateral epiblast (CLE), resulting in body axis posterior elongation. Previous studies of mutants identified genes for posterior extension and vertebral patterning along the anteroposterior axis. Hox gene has been extensively investigated for its expression pattern and transcriptional regulation. In recent years, to elucidate the mechanism that controls the expression patterns of Hox genes, researchers have not only searched for enhancer regions and the transcription factors that bind to them but have also investigated chromatin structure, epigenetics and non‐coding RNA associated with Hox gene expression. These new findings reveal that the previously identified genes essential for posterior body axis elongation of the embryo determine positional information along the anteroposterior axis by induction of Hox genes via enhancer regions. In this review, we focus on genes that control posterior elongation and vertebral patterning along the anteroposterior axis in the PSM and CLE. We first describe the mechanism of maintenance of the stem cell‐like cell populations at the CLE, which is essential for the posterior elongation of the embryo. Next, the factors involved in posterior region formation and patterning of the vertebra are described. Finally, we discuss the regulatory mechanism of Hox gene expression and the mechanism that is responsible for the differences in skeletal pattern between species. [ABSTRACT FROM AUTHOR]

Background: We evaluated the effect of the anteroposterior (AP) axis of the proximal tibia defined at the cutting surface using an image-free navigation system in total knee arthroplasty.Methods: This prospective study included 68 patients (79 knees) who underwent total knee arthroplasty. The tibial AP axis was registered in the navigation system with reference to Akagi's line, connecting the middle of the posterior cruciate ligament to the medial border of the patellar tendon attachment at the tibial joint surface. After proximal tibial osteotomy, the AP axis was replicated as the AP(O) axis. We measured the difference between the AP axis defined at the joint surface and the AP(O) axis defined at the osteotomy surface.Results: The AP(O) axis at the osteotomy surface internally rotated 2.0° to the AP axis at the joint surface, and the AP(O) axis outlier (difference to AP axis: >3°) occurred in 54% (43 knees). In the >3° malrotation group, internal malrotation occurred in 37% (30 knees) and external malrotation occurred in 17% (13 knees). In the outlier analysis, the left knees were significantly found in the internal outlier group.Conclusion: The tibial AP axis, connecting the middle of the posterior cruciate ligament to the medial border of the patellar tendon attachment defined at the tibial joint surface, could not be replicated at the tibial osteotomy surface. If the tibial components were set depending only on the AP axis defined at the osteotomy surface, the tibial components could internally rotate and have more outliers, especially in the left knees. [ABSTRACT FROM AUTHOR]

Purpose: The purpose of this study was to define various anteroposterior axes of the tibial component as references and to evaluate their accuracy and variability using virtual surgery. It was hypothesized that (1) Akagi's Line could result in high accuracy and low variability in varus osteoarthritic knees; (2) anteroposterior axes defined by using the tibial bony cutting surface as a landmark might be good substitutes for Akagi's Line; and (3) extra-articular bony landmarks might influence the variability of the anteroposterior axis.Methods: Three-dimensional bone models were reconstructed from the preoperative computed tomography data of 111 osteoarthritic knees with varus deformities. Seven different anteroposterior axes of the tibial component were defined: Akagi's Line, Axis MED, Axis 1/6MED, Axis 1/3MED, Axis of Oval Shape, Axis of Anterior Crest, and Axis Second Metatarsus. The rotational mismatch angle was measured between the tibial anteroposterior axis and the line perpendicular to the transepicondylar axis projected on the cutting surface (positive value: external rotation of the tibial anteroposterior axis).Results: The average rotational mismatch angles (referring to the projected anatomical/surgical epicondylar axes) were - 2.7° ± 5.8°/1.0° ± 6.0° (Akagi's Line), - 4.2° ± 7.7°/- 0.5° ± 7.8°, 2.9° ± 7.2°/6.6° ± 7.2°, 9.8° ± 7.0°/13.5° ± 6.8° (Axis MED, Axis 1/6MED, Axis 1/3MED), - 5.1° ± 7.9°/- 1.4° ± 7.8° (Axis of Oval Shape), and 19.3 ± 9.5°/23.0° ± 9.6°, - 2.0° ± 11.3°/1.7° ± 11.4° (Axis Anterior Crest, Axis Second Metatarsus), respectively.Conclusions: Akagi's Line provided the best accuracy and least variability in varus osteoarthritic knees. Axis 1/6MED and Axis MED are good substitutes for Akagi's Line due to the difficulty of identifying the attachment site of the posterior cruciate ligament after the proximal tibia has been cut. Extra-articular bony landmarks should not be used for alignment due to their high variability. This study will aid surgeons in choosing the proper anteroposterior axis of the tibial component to reduce rotational mismatch and thus achieve good clinical knee outcomes.Levels Of Evidence: III. [ABSTRACT FROM AUTHOR]

Background: We evaluated the effect of cutting surface on the anteroposterior (AP) axis of the proximal tibia using a 3-dimensional (3D) bone model to ensure proper tibial rotational alignment in total knee arthroplasty.Methods: 3D bone models were reconstructed from the preoperative computed tomography data of 93 Japanese osteoarthritis knees with varus deformity. The AP axis was defined as the perpendicular bisector of the medial and lateral condylar centers in a 3D coordinate system. Bone cutting of the proximal tibia was performed with various tibial posterior slopes (0°, 3°, 7°) to the mechanical axis, and we compared the AP axes before and after bone cutting.Results: The AP axis before bone cutting crossed a point at about 16% (one-sixth) of the distance from the medial edge of the patellar tendon at its tibial attachment. The AP axis after bone cutting was significantly internally rotated at all posterior slopes: 4.1° at slope 0°, 3.0° at slope 3°, and 2.1° at slope 7°. The percentages of cases with differences of more than 3° or 5° were 66.7% and 34.4% at slope 0°, 53.8% and 24.7% at slope 3°, and 38.3% and 11.8% at slope 7°, respectively.Conclusion: The AP axis of the proximal tibia may be rotated internally after resection of the proximal tibia in total knee arthroplasty. Hence, surgeons should recognize the effect of changes in the cutting surface on rotational alignment of the proximal tibia. [ABSTRACT FROM AUTHOR]

The presence of an anteroposterior body axis is a fundamental feature of bilateria. Within this group, echinoderms have secondarily evolved pentameral symmetric body plans. Although all echinoderms present bilaterally symmetric larval stages, they dramatically rearrange their body axis and develop a pentaradial body plan during metamorphosis. Therefore, the location of their anteroposterior body axis in adult forms remains a contentious issue. Unlike other echinoderms, sea cucumbers present an obvious anteroposterior axis not rearranged during metamorphosis, thus representing an interesting group to study their anteroposterior axis patterning. Hox genes are known to play a broadly conserved role in anteroposterior axis patterning in deuterostomes. Here, we report the expression patterns of Hox genes from early development to pentactula stage in sea cucumber. In early larval stages, five Hox genes ( AjHox1, AjHox7, AjHox8, AjHox11/ 13a, and AjHox11/ 13b) were expressed sequentially along the archenteron, suggesting that the role of anteroposterior patterning of the Hox genes is conserved in bilateral larvae of echinoderms. In doliolaria and pentactula stages, eight Hox genes ( AjHox1, AjHox5, AjHox7, AjHox8, AjHox9/ 10, AjHox11/ 13a, AjHox11/ 13b, and AjHox11/ 13c) were expressed sequentially along the digestive tract, following a similar expression pattern to that found in the visceral mesoderm of other bilateria. Unlike other echinoderms, pentameral expression patterns of AjHox genes were not observed in sea cucumber. Altogether, we concluded that AjHox genes are involved in the patterning of the digestive tract in both larvae and metamorphosis of sea cucumbers. In addition, the anteroposterior axis in sea cucumbers might be patterned like that of other bilateria. [ABSTRACT FROM AUTHOR]

Background The alignment of the knee in the transverse plane is important to the biomechanical functions of the lower limb, and is also associated with the outcomes of the total knee arthroplasty. This study aimed to evaluate the dynamic tibiofemoral alignment in the transverse plane during a weight-bearing activity. Methods Knee kinematics of weight-bearing flexion from 0° to 120° was obtained in 16 healthy subjects utilizing biplanar radiography and 3D–2D registration techniques. The anteroposterior axes of the femur at multiple flexion angles in the range of knee motion were used to calculate the anteroposterior axis of motion using the least square method. The latter was compared to six surface-derived anatomical axes in the proximal tibia which were most commonly reported in the literature. The relationship between the anteroposterior axis of motion and the tibial tubercle was also quantified. Findings The anteroposterior axis of motion did not coincide with any of the six anatomical axes tested. Their orientations varied from 10.3° of external rotation to 9.9° of internal rotation in relation to the former. The anteroposterior axis of motion tended to intersect the tibial tubercle between the medial border and the medial 1/3 point. Interpretation Instead of any of the tested anatomical axes, the transverse knee alignment during functional movements is associated with the medial 1/3 portion of the tibial tubercle. This region may be helpful for the rotational alignment of the tibial components in total knee arthroplasty. [ABSTRACT FROM AUTHOR]

In insect embryos, anteroposterior patterning is coordinated by the sequential expression of the 'timer' genes caudal , Dichaete, and odd-paired , whose expression dynamics correlate with the mode of segmentation. In Drosophila , the timer genes are expressed broadly across much of the blastoderm, which segments simultaneously, but their expression is delayed in a small 'tail' region, just anterior to the hindgut, which segments during germband extension. Specification of the tail and the hindgut depends on the terminal gap gene tailless , but beyond this the regulation of the timer genes is poorly understood. We used a combination of multiplexed imaging, mutant analysis, and gene network modelling to resolve the regulation of the timer genes, identifying 11 new regulatory interactions and clarifying the mechanism of posterior terminal patterning. We propose that a dynamic Tailless expression gradient modulates the intrinsic dynamics of a timer gene cross-regulatory module, delineating the tail region and delaying its developmental maturation., Competing Interests: EC, MB, MB No competing interests declared, (© 2022, Clark et al.)

Retinoic acid ( RA), the most potent natural form of vitamin A, is a key morphogen in vertebrate development and a potent regulator of both adult and embryonic cell differentiation. Specifically, RA regulates clustered Hox gene expression during embryogenesis and is required to establish the anteroposterior body plan. The PI3K/Akt pathway was also reported to play an essential role in the process of RA-induced cell differentiation. Therefore, we tested whether the PI3K/Akt pathway is involved in RA-induced Hox gene expression in a F9 murine embryonic teratocarcinoma cells. To examine the effect of PI3K/Akt signaling on RA-induced initiation of collinear expression of Hox genes, F9 cells were treated with RA in the presence or absence of PI3K inhibitor LY294002, and time-course gene expression profiles for all 39 Hox genes located in four different clusters- Hoxa, Hoxb, Hoxc, and Hoxd-were analyzed. Collinear expression of Hoxa and - b cluster genes was initiated earlier than that of the - c and - d clusters upon RA treatment. When LY294002 was applied along with RA, collinear expression induced by RA was delayed, suggesting that the PI3K/Akt signaling pathway somehow regulates RA-induced collinear expression of Hox genes in F9 cells. The initiation of Hox collinear expression by RA and the delayed expression following LY294002 in F9 cells would provide a good model system to decipher the yet to be answered de novo collinear expression of Hox genes during gastrulation, which make the gastrulating cells to remember their positional address along the AP body axis in the developing embryo. [ABSTRACT FROM AUTHOR]

Highlights: [•] Contestation that Winter et al.’s (1993) model can be used in any condition. [•] Experimental confirmation of our contestation. [•] Deep analysis of the amplitude and active contributions of the mechanisms. [•] Proposition of methodological requirements to use Winter et al.’s model. [Copyright &y& Elsevier]

Introduction: Correct rotational alignment of the tibial component is crucial for total knee arthroplasty (TKA). Several studies have indicated that the best rotational orientation of the tibial component is close to the medial border of the tibial tubercle. However, it remains obscure whether it is always right. Thus, the objective of current study was to quantify tibial rotational alignment in 120 primary rotating platform TKAs using the medial border of tibial tubercle as a landmark between July 2008 and June 2010. Methods: The femoral component was positioned parallel to the transepicondlylar axis, and a rotating platform trial insert was used to determine tibial insert rotational alignment relative to the most medial aspect of the tibial tubercle with the knee in full extension. Rotational alignment of the components was detected based on radiograph and CT scan. This investigation is based on the premise that all neutral points would lie within 10° of the mean. Results: The mean divergence external to the medial border of the tubercle was 2.3°±3.5°. However, six of the knees (5%) had neutral points ≥10° from the mean, including two valgus knees measured 10° of internal rotation and four varus knees measured 10° of external rotation. Conclusion: Using the medial border of tibial tubercle as a landmark does not always result in a good femorotibial rotational alignment. Surgeons using fixed bearings component should be aware of this effect to avoid suboptimal outcomes resulting from tibiofemoral rotational malalignment in full extension. Level of evidence: Diagnostic study, Level II-3. [ABSTRACT FROM AUTHOR]

Background: The traditional anteroposterior (AP) axis (i.e., Akagi's line) has been widely used as the tibial component AP axis during total knee arthroplasty (TKA). However, this AP axis has been defined based on computed tomography (CT) in a non-weight-bearing supine position. In this study, AP axes of the tibial plateau from upright CT in weight-bearing and non-weight-bearing positions were determined and compared., Methods: This study included 43 knees from 23 healthy volunteers. CT images were obtained in weight-bearing and non-weight-bearing standing positions using a 320-detector row upright CT scanner. The line perpendicular to surgical transepicondylar axis projected onto the tibia plateau was determined as the AP axis in upright weight-bearing and non-weight-bearing conditions. Angular differences between these two conditions were measured., Results: The upright weight-bearing AP axis was positioned in a mean of 7.4 ± 4.3° of internal rotation relative to the traditional AP axis. Distance between the traditional and upright weight-bearing AP axis was 2.9 ± 1.6 mm at the edge of the tibial plateau. The upright non-weight-bearing AP axis was positioned in a mean of 3.5 ± 4.1° of internal rotation relative to the traditional AP axis. Mean angular difference between weight-bearing and non-weight-bearing conditions was 3.9 ± 4.1°., Conclusions: The upright weight-bearing AP axis was positioned in 7.4° of internal rotation relative to the traditional AP axis, showing one-seventh of the tibial tuberosity away from the medial border of the tibial tubercle, which represents a practical landmark for the tibial component AP axis during TKA., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022. Published by Elsevier B.V.)

Despite long-standing interest, the molecular mechanisms underlying the establishment of anterior-posterior (AP) polarity remain among the unsolved mysteries in metazoans. In the planarians (a family of flatworms), canonical Wnt/β-catenin signaling is required for posterior specification, as it is in many animals. However, the molecular mechanisms regulating the posterior-specific induction of Wnt genes according to the AP polarity have remained unclear. Here, we demonstrate that Hedgehog (Hh) signaling is responsible for the establishment of AP polarity via its regulation of the transcription of Wnt family genes during planarian regeneration. We found that RNAi gene knockdown of Dugesia japonica patched (Djptc) caused ectopic tail formation in the anterior blastema of body fragments, resulting in bipolar-tails regeneration. In contrast, RNAi of hedgehog (Djhh) and gil (Digli) caused bipolar-heads regeneration. We show that Patched-mediated Hh signaling was crucial for posterior specification, which is established by regulating the transcription of Wnt genes via downstream Gli activity. Moreover, differentiated cells were responsible for the posterior specification of undifferentiated stem cells through Wnt/β-catenin signaling. Surprisingly, Djhh was expressed in neural cells all along the ventral nerve cords (along the AP axis), but not in the posterior blastema of body fragments, where the expression of Wnt genes was induced for posteriorization. We therefore propose that Hh signals direct head or tail regeneration according to the AP polarity, which is established by Hh signaling activity along the body's preexisting nervous system. [ABSTRACT FROM AUTHOR]

Regeneration requires specification of the identity of new tissues to be made. Whether this process relies only on intrinsic regulative properties of regenerating tissues or whether wound signaling provides input into tissue repatterning is not known. The headversus-tail regeneration polarity decision in planarians. which requires Wnt signaling, provides a paradigm to study the process of tissue identity specification during regeneration. The Smed-wntP-1 gene is required for regeneration polarity and is expressed at the posterior pole of intact animals. Surprisingly, wntP-1 was expressed at both anteriorand posterior-facing wounds rapidly after wounding. wntP-1 expression was induced by all types of wounds examined, regardless of whether wounding prompted tail regeneration. Regeneration polarity was found to require new expression of wntP-1. Inhibition of the wntP-2 gene enhanced the polarity phenotype due to wntP-1 inhibition, with new expression of wntP-2 in regeneration occurring subsequent to expression of wntP-1 and localized only to posterior-facing wounds. New expression of wntP-2 required wound-induced wntP-1. Finally, wntP-1 and wntP-2 expression changes occurred even in the absence of neoblast stem cells, which are required for regeneration. suggesting that the role of these genes in polarity is independent of and instructive for tail formation. These data indicate that wound-induced input is involved in resetting the normal polarized features of the body axis during regeneration. [ABSTRACT FROM AUTHOR]

Abstract: Sox7, -17 and -18 constitute the Sox subgroup F (SoxF) of HMG box transcription factor genes, which all are co-expressed in developing vascular endothelial cells in mice. Here we characterized cardiovascular phenotypes of Sox17/Sox18-double and Sox17-single null embryos during early-somite stages. Whole-mount PECAM staining demonstrated the aberrant heart looping, enlarged cardinal vein and mild defects in anterior dorsal aorta formation in Sox17 single-null embryos. The Sox17/Sox18 double-null embryos showed more severe defects in formation of anterior dorsal aorta and head/cervical microvasculature, and in some cases, aberrant differentiation of endocardial cells and defective fusion of the endocardial tube. However, the posterior dorsal aorta and allantoic microvasculature was properly formed in all of the Sox17/Sox18 double-null embryos. The anomalies in both anterior dorsal aorta and head/cervical vasculature corresponded with the weak Sox7 expression sites. This suggests the region-specific redundant activities of three SoxF members along the anteroposterior axis of embryonic vascular network. [Copyright &y& Elsevier]

Abstract: The appropriate regulation of retinoic acid signaling is indispensable for patterning of the vertebrate central nervous system along the anteroposterior (A–P) axis. Although both CYP26A1 and CYP26C1, retinoic acid-degrading enzymes that are expressed at the anterior end of the gastrulating mouse embryo, have been thought to play an important role in central nervous system patterning, the detailed mechanism of their contribution has remained largely unknown. We have now analyzed CYP26A1 and CYP26C1 function by generating knockout mice. Loss of CYP26C1 did not appear to affect embryonic development, suggesting that CYP26A1 and CYP26C1 are functionally redundant. In contrast, mice lacking both CYP26A1 and CYP26C1 were found to manifest a pronounced anterior truncation of the brain associated with A–P patterning defects that reflect expansion of posterior identity at the expense of anterior identity. Furthermore, Cyp26a1 −/− Cyp26c1 −/− mice fail to produce migratory cranial neural crest cells in the forebrain and midbrain. These observations, together with a reevaluation of Cyp26a1 mutant mice, suggest that the activity of CYP26A1 and CYP26C1 is required for correct A–P patterning and production of migratory cranial neural crest cells in the developing mammalian brain. [Copyright &y& Elsevier]

Abstract: This article focuses on the interphyletic comparison of gene expression patterns. By means of the hypothesis of the inversion of the dorsoventral axis during the evolution of the Bilateria, it is demonstrated, that evolutionary developmental biologists use similarities in spatial and temporal gene expression patterns as evidence for the formulation of hypotheses of homology concerning either developing structures or body regions. The molecular genetic and morphogenetic evidence used is discussed within the framework of a cladistic-phylogenetic analysis based on the phylogenetic tree of the Bilateria. I argue that similarity of spatial and temporal gene expression patterns is not a sufficient criterion for homology inference. Therefore, gene expression patterns should be coded as characters. Their homology should be tested in concert with other characters. Furthermore, it is demonstrated, that spatial and temporal similar gene expression patterns, indicating similar molecular genetic mechanisms, were interpreted as an analytical criterion of homology, offering the possibility to identify similar structures. In contrast to this, the evolutionary developmental biolgists have not developed a causal-analytically extended concept of shape, from which a causal-analytical concept of homology could be deduced. Instead, the homology concept from evolutionary morphology is used. [Copyright &y& Elsevier]

Abstract: Testis induction is associated with gonadal Sry and Sox9 expression in mammals. This study investigated whether Sry expression directly induces male-specific Sox9 activation during early phases of testis differentiation. We have established an XX sex-reversal mouse line carrying the Sry transgene driven by a weak basal promoter of the Hsp70.3 gene (Hsp-Sry), whereby the transgene was activated in the gonads along the entire anteroposterior axis from earlier stages. The effects of misexpression and overexpression of Sry on the spatiotemporal pattern of Sox9 expression were examined using both XX and XY gonads of Hsp-Sry transgenic embryos. It was shown that ectopic expression of Sry transcripts in the entire gonadal area from earlier stages promotes neither any advance in the timing nor any appreciable ectopic activation of endogenous Sox9 expression. Immediately after the onset of Sox9 activation, however, both the level of Sox9 expression and the number of SOX9-positive cells were significantly enhanced in Hsp-Sry/XY gonads, as compared with those in wild-type/XY and Hsp-Sry/XX gonads. These findings suggest that, although Sry is capable of up-regulating Sox9 expression dose-dependently, Sry mRNA expression alone is not likely to provide positional or timing information needed for male-specific Sox9 activation in developing XY gonads. [Copyright &y& Elsevier]

Gene expression profiling of β-catenin, Cripto and Wnt3 mutant mouse embryos has been used to characterise the genetic networks that regulate early embryonic development. We have defined genes whose expression is regulated by β-catenin during formation of the anteroposterior axis and the mesoderm, and have identified Cripto, which encodes a Nodal co-receptor, as a primary target of β-catenin signals both in embryogenesis as well as in colon carcinoma cell lines and tissues. We have also defined groups of genes regulated by Wnt3/β-catenin signalling during primitive streak and mesoderm formation. Our data assign a key role to β-catenin upstream of two distinct gene expression programs during anteroposterior axis and mesoderm formation. [ABSTRACT FROM AUTHOR]

Many chordate-specific morphological features develop depending on retinoic acid (RA). We isolated cDNA clones encoding a retinoic acid receptor (CiRAR) and a retinoid X receptor (CiRXR) in the ascidian Ciona intestinalis. CiRAR mRNA was detected in the anterior ectoderm and endoderm during gastrulation. The expression persists in the head endoderm and two discrete regions of the nerve cord in the tailbud embryo. CiRXR mRNA was ubiquitously expressed. RA affected closure of the neural tube and formation of the adhesive papillae. However, no obvious upregulation in CiRAR expression was observed. Expression of some, but not all, of the neural and papilla-specific genes was reduced in the RA-treated embryo. These results suggest limited roles of CiRAR in ascidian embryos. [Copyright &y& Elsevier]

To clarify connective-tissue-specific genes involved in adult epithelial development during amphibian intestinal remodeling, we have isolated 16 cDNA clones derived from the anterior part of Xenopus laevis intestine cultured in vitro by using subtractive suppression hybridization. Among four genes identified, the expression of Xtld, a Xenopus homolog of Drosophila Tolloid closely related to bone morphogenic protein-1 (BMP-1), was most remarkably up-regulated during metamorphosis. To further explore the roles of Xtld in intestinal remodeling, we examined its developmental expression in the X. laevis intestine by in situ hybridization and northern blot analysis. Xtld mRNA first became detectable in the connective tissue just before the appearance of adult epithelial primordia. Subsequently, the level of Xtld mRNA reached a high in the connective tissue, concomitantly with adult epithelial development along the anteroposterior axis of the intestine. Thereafter, towards the completion of metamorphosis, the expression of Xtld mRNA was down-regulated. Thus, the expression profile of Xtld mRNA spatiotemporally correlates well with adult epithelial development in vivo. Furthermore, the present culture study has shown that thyroid hormone (TH) up-regulates the expression of Xtld mRNA organ-autonomously in the anterior part of the intestine, but not in its posterior part, and that TH up-regulation of Xtld expression is not mediated by the epithelium. These results suggest that TH directly up-regulates Xtld expression in the connective tissue along the anteroposterior axis, which in turn plays important roles in adult epithelial development during amphibian intestinal remodeling. [ABSTRACT FROM AUTHOR]

Ectoderm pieces explanted from embryos of Xenopus laevis were cultured and examined for differentiation of hatching gland cells, using immunoreactivity against anti-XHE (Xenopus hatching enzyme) as a marker. The anterio-dorsal ectoderm excised from stage 12–13 (mid–late gastrula) embryos developed hatching gland cells. Meanwhile, the posterio-, but not the anterio-dorsal ectoderm from stage 11 (early gastrula) embryos developed these cells, although it is not fated to do so during normogenesis. This hatching gland cell differentiation from stage 11 posterior ectoderm was not affected by conjugated sandwich culture with the mesoderm but was suppressed when explants contained an anterior portion of the ectoderm. Conjugated cultures of anterior and posterior portions of the ectoderm in various combinations indicated that differentiation of hatching gland cells from stage 11 posterior and stage 12 anterior portions was suppressed specifically by stage 11 anterior ectoderm. Northern blot analyses of cultured explants showed that XHE was expressed in association with XA-1, suggesting its dependence on the anteriorized state. These results indicate that the planar signal(s) emanating from stage 11 anterior ectoderm participates in suppression of the expression of the anteriorized phenotype so that an ordered differentiation along the anteroposterior axis of the surface ectoderm is accomplished. [ABSTRACT FROM AUTHOR]

Tailless is a committed transcriptional repressor and principal regulator of the brain and eye development in Drosophila . Rpd3, the histone deacetylase, is an established repressor that interacts with co-repressors like Sin3a, Prospero, Brakeless and Atrophin. This study aims at deciphering the role of Rpd3 in embryonic segmentation and larval brain development in Drosophila . It delineates the mechanism of Tailless regulation by Rpd3 , along with its interacting partners. There was a significant reduction in Tailless in Rpd3 heteroallelic mutant embryos, substantiating that Rpd3 is indispensable for the normal Tailless expression. The expression of the primary readout, Tailless was correlative to the expression of the neural cell adhesion molecule homologue, Fascilin2 (Fas2). Rpd3 also aids in the proper development of the mushroom body. Both Tailless and Fas2 expression are reported to be antagonistic to the epidermal growth factor receptor (EGFR) expression. The decrease in Tailless and Fas2 expression highlights that EGFR is upregulated in the larval mutants, hindering brain development. This study outlines the axis comprising Rpd3, dEGFR, Tailless and Fas2, which interact to fine-tune the early segmentation and larval brain development. Therefore, Rpd3 along with Tailless has immense significance in early embryogenesis and development of the larval brain.