Anteroposterior Patterning Research Articles

A comparative analysis of fibroblast growth factor receptor signalling during Xenopus development.

The fibroblast growth factor (FGF) signalling system of vertebrates is complex. In common with other vertebrates, secreted FGF ligands of the amphibian Xenopus signal through a family of four FGF receptor tyrosine kinases (fgfr1, 2, 3 and 4). A wealth of previous studies has demonstrated important roles for FGF signalling in regulating gene expression during cell lineage specification in amphibian development. In particular, FGFs have well-established roles in regulating mesoderm formation, neural induction and patterning of the anteroposterior axis. However, relatively little is known regarding the role of individual FGFRs in regulating FGF-dependent processes in amphibian development. In this study we make use of synthetic drug inducible versions of Xenopus Fgfr1, 2 and 4 (iFgfr1, 2 and 4) to undertake a comparative analysis of their activities in the tissues of the developing embryo. We find that Xenopus Fgfr1 and 2 have very similar activities. Both Fgfr1 and Fgfr2 are potent activators of MAP kinase ERK signalling, and when activated in the embryo during gastrula stages regulate similar cohorts of transcriptional targets. In contrast, Fgfr4 signalling in naïve ectoderm and neuralised ectoderm activates ERK signalling only weakly compared to Fgfr1/2. Furthermore, our analyses indicate that in Xenopus neural tissue the Fgfr4 regulated transcriptome is very different from that of Fgfr1. We conclude that signalling downstream of Fgfr1 and 2 regulates similar processes in amphibian development. Interestingly, many of the previously identified canonical transcriptional targets of FGF regulation associated with germ layer specification and patterning are regulated by Fgfr1/Fgfr2 signalling. In contrast, the downstream consequences of Fgfr4 signalling are different, although roles for Fgfr4 signalling in lineage specification and anteroposterior patterning are also indicated.

Ashwin Gene Expression Profiles in Oocytes, Preimplantation Embryos, and Fetal and Adult Bovine Tissues.

Simple SummaryAshwin is a gene involved in the morphogenesis of the central nervous system and the early embryonic development of Xenopus laevis. The analysis of its phylogeny in silico has shown that its functions are restricted to vertebrates, but we lack additional information regarding its biological importance in higher vertebrates, such as mammals. The present study reveals the wide and variable expression of this gene in different bovine organs and confirms its significant expression during early embryonic development, with a pattern similar to that reported for maternal genes. In addition, specific expression of this gene throughout follicular development and during bovine spermatogenesis is revealed, leading to the proposal of ashwin as a new gene with important biological implications in bovine development and reproduction.The ashwin gene, originally identified in Xenopus laevis, was found to be expressed first in the neural plate and later in the embryonic brain, eyes, and spinal cord. Functional studies of ashwin suggest that it participates in cell survival and anteroposterior patterning. Furthermore, ashwin is expressed zygotically in this species, which suggests that it participates in embryonic development. Nevertheless, the expression of this gene has not been studied in mammals. Thus, the aim of this study was to analyze the ashwin expression pattern in bovine fetal and adult tissues, as well as in three independent samples of immature and mature oocytes, and in two- to four-, and eight-cell embryos, morula, and blastocysts. Spatiotemporal expression was analyzed using real-time polymerase chain reaction (PCR); ashwin mRNA was detected in all tissues analyzed, immature and mature oocytes, and two- to eight-cell embryos. It was down-regulated in morula and blastocysts, suggesting that this expression profile is similar to that of maternal genes. Immunohistochemical localization of the ashwin protein in fetal and adult ovaries and testes reveals that this protein is consistently present during all stages of follicular development and during bovine spermatogenesis. These observations lead us to propose ashwin as an important gene involved in mammalian reproduction.

Structural, morphometric and immunohistochemical study of the rabbit accessory olfactory bulb.

The accessory olfactory bulb (AOB) is the first neural integrative centre of the vomeronasal system (VNS), which is associated primarily with the detection of semiochemicals. Although the rabbit is used as a model for the study of chemocommunication, these studies are hampered by the lack of knowledge regarding the topography, lamination, and neurochemical properties of the rabbit AOB. To fill this gap, we have employed histological stainings: lectin labelling with Ulex europaeus (UEA-I), Bandeiraea simplicifolia (BSI-B4), and Lycopersicon esculentum (LEA) agglutinins, and a range of immunohistochemical markers. Anti-G proteins Gαi2/Gαo, not previously studied in the rabbit AOB, are expressed following an antero-posterior zonal pattern. This places Lagomorpha among the small groups of mammals that conserve a double-path vomeronasal reception. Antibodies against olfactory marker protein (OMP), growth-associated protein-43 (GAP-43), glutaminase (GLS), microtubule-associated protein-2 (MAP-2), glial fibrillary-acidic protein (GFAP), calbindin (CB), and calretinin (CR) characterise the strata and the principal components of the BOA, demonstrating several singular features of the rabbit AOB. This diversity is accentuated by the presence of a unique organisation: four neuronal clusters in the accessory bulbar white matter, two of them not previously characterised in any species (the γ and δ groups). Our morphometric study of the AOB has found significant differences between sexes in the numerical density of principal cells, with larger values in females, a pattern completely opposite to that found in rats. In summary, the rabbit possesses a highly developed AOB, with many specific features that highlight the significant role played by chemocommunication among this species.

Caudal Type Homeobox 2 Is Required for Leukemogenesis but Not for Normal Hematopoieisis

Caudal Type Homeobox 2 (CDX2) is a caudal-related homeobox family transcription factor known to be developmental regulator involved in murine axial elongation and anteroposterior vertebral patterning and cell fate determination in the intestine. In adults, CDX2 expression is restricted to the small intestine and the colon. Interestingly, CDX2 is overexpressed in ~90% of human acute myeloid leukemias and the majority of acute lymphoblastic leukemias. Hence, aberrant expression of CDX2 may play a contributing role in leukemogenesis. The role of CDX2 in normal hematopoietic development is unknown. To assess the role of CDX2 in normal hematopoiesis we characterized hematopoietic development in Cdx2 fl/fl Mx1-Cre+ mice after poly (I:C)-mediated gene deletion compared to wildtype littermates. Under steady state conditions, no significant defects were identified in long-term hematopoietic stem cells (LT-HSCs), multipotent progenitors, myeloid progenitors, or mature cell lineages. To test if long-term hematopoietic stem cells were functionally impaired following Cdx2 deletion, competitive transplantation assays were performed. We found that CDX2 was not required for long-term hematopoietic reconstitution in the competitive transplant setting. Together, these data establish that CDX2 is not required for adult steady state hematopoiesis or LT-HSC function. We then asked whether or not CDX2 was essential for leukemogenesis. To interrogate this, Cdx2 fl/fl Mx1-Cre+, Cdx2 fl/+ Mx1-Cre+, and wildtype littermates were treated with poly (I:C) to facilitate gene deletion or for control purposes. Bone marrow cells from the mice were then transformed using well-established HOXA9/MEIS1 or MLL-AF10 leukemogenesis models. In both systems, Cdx2-deficiency prevented leukemia development, whereas wildtype controls succumbed to leukemia within 200 days. Cdx2 heterozygous knockout animals had a delayed onset of leukemia compared to wildtype animals. Taken together, these data indicate that CDX2 is not required for steady state adult hematopoiesis or LT-HSC function, but is necessary for the development of leukemia. Our findings suggest CDX2 has potential as a novel therapeutic target that could be exploited in the majority of AML and ALL patients across a broad mutational spectrum. The nomination of CDX2 as a key target for the majority of leukemias is significant, as current targeted treatment strategies are limited to only particular patient subsets. Disclosures No relevant conflicts of interest to declare.

Fgf-signaling is compartmentalized within the mesenchyme and controls proliferation during salamander limb development.

Although decades of studies have produced a generalized model for tetrapod limb development, urodeles deviate from anurans and amniotes in at least two key respects: their limbs exhibit preaxial skeletal differentiation and do not develop an apical ectodermal ridge (AER). Here, we investigated how Sonic hedgehog (Shh) and Fibroblast growth factor (Fgf) signaling regulate limb development in the axolotl. We found that Shh-expressing cells contributed to the most posterior digit, and that inhibiting Shh-signaling inhibited Fgf8 expression, anteroposterior patterning, and distal cell proliferation. In addition to lack of a morphological AER, we found that salamander limbs also lack a molecular AER. We found that amniote and anuran AER-specific Fgfs and their cognate receptors were expressed entirely in the mesenchyme. Broad inhibition of Fgf-signaling demonstrated that this pathway regulates cell proliferation across all three limb axes, in contrast to anurans and amniotes where Fgf-signaling regulates cell survival and proximodistal patterning.

AN ANATOMICAL STUDY ON HILAR VARIATIONS AND MORPHOMETRIC DIMENSIONS OF HUMAN KIDNEYS

Variations in renal hilar arrangement patterns and morphometric dimensions are clinically relevant in this age of advancing modern medicine and minimally invasive surgery. The purpose of the present study is to record variations in renal hilar arrangement patterns and assess renal dimensions of length, width and thickness respectively. Hilar regions of fifty isolated embalmed kidneys were carefully dissected and variations observed were photographed and documented. Renal dimensions were measured with digital calipers and values obtained were tabulated and analysed. Normal anteroposterior hilar arrangement pattern was observed in 72% cases. Anterior and posterior divisions of renal artery were observed in 24% cases with anterior division being the most anteriorly placed structure in 14% cases. The renal pelvis was situated between the divisions of the renal artery in 8% cases. Prehilar segmental branches anterior to renal vein were observed in 4% cases. Other variations seen included extrahilar branches (4%), superior polar artery arising from anterior division of renal artery, prehilar tributaries of renal vein and an additional renal artery in 1 case each. The mean renal length was 9.35+/- 0.98 cm for right and 9.25 +/- 1.25 cm for left kidneys, mean renal width 4.93 +/- 0.65 cm for right and 4.95 +/- 0.5 cm for left kidneys and mean renal thickness 3.77 +/- 0.7 cm for right and 3.86 +/- 0.53 cm for left kidneys respectively. No statistically significant difference was observed in the mean values between right and left sides. The clinical implications of these findings have been discussed. The findings of this study may enhance the existing literature and contribute additional information for improving treatment outcomes during clinical and surgical interventions.
 Keywords: Variation, Hilum, Kidneys, Morphometry, Arrangement pattern, dimensions

Pattern of fin rays along the antero-posterior axis based on their connection to distal radials

BackgroundTeleost paired fins are composed of two endoskeletal domains, proximal and distal radials, and an exoskeletal domain, the fin ray. The zebrafish pectoral fin displays elaborately patterned radials along the anteroposterior (AP) axis. Radials are considered homologous to tetrapod limb skeletons, and their patterning mechanisms in embryonic development are similar to those of limb development. Nevertheless, the pattern along the AP axis in fin rays has not been well described in the zebrafish pectoral fin, although several recent reports have revealed that fin ray development shares some cellular and genetic properties with fin/limb endoskeleton development. Thus, fin ray morphogenesis may involve developmental mechanisms for AP patterning in the fin/limb endoskeleton, and may have a specific pattern along the AP axis.ResultsWe conducted detailed morphological observations on fin rays and their connection to distal radials by comparing intra- and inter-strain zebrafish specimens. Although the number of fin rays varied, pectoral fin rays could be categorized into three domains along the AP axis, according to the connection between the fin rays and distal radials; additionally, the number of fin rays varied in the posterior part of the three domains. This result was confirmed by observation of the morphogenesis process of fin rays and distal radials, which showed altered localization of distal radials in the middle domain. We also evaluated the expression pattern of lhx genes, which have AP patterning activity in limb development, in fin rays and during distal radial development and found these genes to be expressed during morphogenesis in both fin rays and distal radials.ConclusionThe fin ray and its connection to the endoskeleton are patterned along the AP axis, and the pattern along the AP axis in the fin ray and the radial connection is constructed by the developmental mechanism related to AP patterning in the limb/fin bud. Our results indicate the possibility that the developmental mechanisms of fin rays and their connection are comparable to those of the distal element of the limb skeleton.

The Transcription Factor Deaf1 Modulates Engrailed-1 Expression to Regulate Skin Appendage Fate

The Transcription Factor Deaf1 Modulates Engrailed-1 Expression to Regulate Skin Appendage Fate

Anteroposterior patterning of the zebrafish ear through Fgf- and Hh-dependent regulation of hmx3a expression

In the zebrafish, Fgf and Hh signalling assign anterior and posterior identity, respectively, to the poles of the developing ear. Mis-expression of fgf3 or inhibition of Hh signalling results in double-anterior ears, including ectopic expression of hmx3a. To understand how this double-anterior pattern is established, we characterised transcriptional responses in Fgf gain-of-signalling or Hh loss-of-signalling backgrounds. Mis-expression of fgf3 resulted in rapid expansion of anterior otic markers, refining over time to give the duplicated pattern. Response to Hh inhibition was very different: initial anteroposterior asymmetry was retained, with de novo duplicate expression domains appearing later. We show that Hmx3a is required for normal anterior otic patterning, and that otic patterning defects in hmx3a-/- mutants are a close phenocopy to those seen in fgf3-/- mutants. However, neither loss nor gain of hmx3a function was sufficient to generate full ear duplications. Using our data to infer a transcriptional regulatory network required for acquisition of otic anterior identity, we can recapitulate both the wild-type and the double-anterior pattern in a mathematical model.

New roles for Wnt and BMP signaling in neural anteroposterior patterning.

During amphibian development, neural patterning occurs via a two-step process. Spemann's organizer secretes BMP antagonists that induce anterior neural tissue. A subsequent caudalizing step re-specifies anterior fated cells to posterior fates such as hindbrain and spinal cord. The neural patterning paradigm suggests that a canonical Wnt-signaling gradient acts along the anteroposterior axis to pattern the nervous system. Wnt activity is highest in the posterior, inducing spinal cord, at intermediate levels in the trunk, inducing hindbrain, and is lowest in anterior fated forebrain, while BMP-antagonist levels are constant along the axis. Our results in Xenopus laevis challenge this paradigm. We find that inhibition of canonical Wnt signaling or its downstream transcription factors eliminates hindbrain, but not spinal cord fates, an observation not compatible with a simple high-to-low Wnt gradient specifying all fates along the neural anteroposterior axis. Additionally, we find that BMP activity promotes posterior spinal cord cell fate formation in an FGF-dependent manner, while inhibiting hindbrain fates. These results suggest a need to re-evaluate the paradigms of neural anteroposterior pattern formation during vertebrate development.

Antero-posterior ectoderm patterning by canonical Wnt signaling during ascidian development.

Wnt/β-catenin signaling is an ancient pathway in metazoans and controls various developmental processes, in particular the establishment and patterning of the embryonic primary axis. In vertebrates, a graded Wnt activity from posterior to anterior endows cells with positional information in the central nervous system. Recent studies in hemichordates support a conserved role for Wnt/β-catenin in ectoderm antero-posterior patterning at the base of the deuterostomes. Ascidians are marine invertebrates and the closest relatives of vertebrates. By combining gain- and loss-of-function approaches, we have determined the role of Wnt/β-catenin in patterning the three ectoderm derivatives of the ascidian Ciona intestinalis, central nervous system, peripheral nervous system and epidermis. Activating Wnt/β-catenin signaling from gastrulation led to a dramatic transformation of the ectoderm with a loss of anterior identities and a reciprocal anterior extension of posterior identities, consistent with studies in other metazoans. Surprisingly, inhibiting Wnt signaling did not produce a reciprocal anteriorization of the embryo with a loss of more posterior identities like in vertebrates and hemichordate. Epidermis patterning was overall unchanged. Only the identity of two discrete regions of the central nervous system, the anteriormost and the posteriormost regions, were under the control of Wnt. Finally, the caudal peripheral nervous system, while being initially Wnt dependent, formed normally. Our results show that the Ciona embryonic ectoderm responds to Wnt activation in a manner that is compatible with the proposed function for this pathway at the base of the deuterostomes. However, possibly because of its fast and divergent mode of development that includes extensive use of maternal determinants, the overall antero-posterior patterning of the Ciona ectoderm is Wnt independent, and Wnt/β-catenin signaling controls the formation of some sub-domains. Our results thus indicate that there has likely been a drift in the developmental systems controlling ectoderm patterning in the lineage leading to ascidians.

Developmental regulation of Wnt signaling by Nagk and the UDP-GlcNAc salvage pathway

In a screen for human kinases that regulate Xenopus laevis embryogenesis, we identified Nagk and other components of the UDP-GlcNAc glycosylation salvage pathway as regulators of anteroposterior patterning and Wnt signaling. We find that the salvage pathway does not affect other major embryonic signaling pathways (Fgf, TGFβ, Notch, or Shh), thereby demonstrating specificity for Wnt signaling. We show that the role of the salvage pathway in Wnt signaling is evolutionarily conserved in zebrafish and Drosophila. Finally, we show that GlcNAc is essential for the growth of intestinal enteroids, which are highly dependent on Wnt signaling for growth and maintenance. We propose that the Wnt pathway is sensitive to alterations in the glycosylation state of a cell and acts as a nutritional sensor in order to couple growth/proliferation with its metabolic status. We also propose that the clinical manifestations observed in congenital disorders of glycosylation (CDG) in humans may be due, in part, to their effects on Wnt signaling during development.

Ci-hox12 tail gradient precedes and participates in the control of the apoptotic-dependent tail regression during Ciona larva metamorphosis

At the onset of the Ciona intestinalis metamorphosis, the first event is tail regression characterized, by a contraction, an apoptotic wave and Primordial Germ Cells (PGC) movement. All these cell behaviors originate from the posterior tail tip and progress to the anterior. Interestingly, earlier in Ciona development, the antero-posterior (A/P) patterning of the tailbud epidermis depends on two antagonist gradients, respectively FGF/MAPK at the posterior and retinoic acid (RA) at the anterior part of the tail. Fundamental genes such as Ci-hox1, Ci-hox12 and Ci-wnt5, classically involved in chordates A/P polarity and patterning, are controlled by these gradients and exhibit specific expression profiles in the tail epidermis. In this study, we first confirmed by video-microscopy that tail regression depends on a postero-anterior wave of a caspase-dependent apoptosis coupled with a contraction event. Concomitantly an apoptotic-dependent postero-anterior movement of PGC was observed for the first time. Unexpectedly, we observed that expression of the posterior hox gene, Ci-hox12, was extended from a posterior localization to the entire tail epidermis as the larvae progress from the swimming period to the settlement stage. In addition, when we disturbed FGF/MAPK or RA gradients we observed strong effects on Ci-hox12 expression pattern coupled with modulation on the subsequent tail regression dynamics. These results support the idea that Ci-hox12 expression in larval tail precedes and participates in the regulation of the postero-anterior cell behavior during the subsequent tail regression.

The Synarcual of the Little Skate, Leucoraja erinacea: Novel Development Among the Vertebrates

Evolutionary variation in anteroposterior patterning of the axial skeleton is a major contributor to the evolution of the vertebrate body plan, with five canonical vertebral types in tetrapods (cervical, thoracic, lumbar, sacral, caudal). However, less is known about the evolutionary origin and variation in vertebral regionalization patterns outside of tetrapods where described vertebral types range from as few as two in some chondrichthyans to eight or more in some teleost fishes. The synarcual is a specialized adaptation of the anterior axial skeleton comprising a putatively fused array of vertebral elements characteristic of jawed vertebrate (gnathostome) clades such as batoid and chimaeroid chondrichthyans where they support enlarged pectoral fins and dorsal fin spines respectively, as well as a fossil group known as the placoderms. Placoderms represent the phylogenetically most basal jawed vertebrates and the presence of a synarcual in these and chondrichthyans may suggest a conserved vertebral type for jawed vertebrates, predating the divergence of stem and crown gnathostomes. Alternatively, synarcuals may have evolved independently in these lineages, exhibiting a remarkable case of morphological convergence. In order to address this question, we investigated the early development of the cervicothoracic synarcual of an emerging model chondrichthyan: the Little skate Leucoraja erinacea. By combining x-ray computed tomography, and classical histology, we show that the skate synarcual is a complex composite element which develops from a hollow, continuous cartilaginous element devoid of any vertebral centra anterior to the pectoral girdle, and fusion/remodeling of initially distinct vertebrae posteriorly. A de novo transcriptome assembly for two developmental stages of the skate synarcual and post-synarcual axial skeletal elements supported this two-phase development, with differences in expression levels of several developmental genes, including Hox family transcription factors, which suggest anterior-posterior regionalization along the vertebral column, potentially linked to the synarcual. In addition, multiple genes related to skeletal remodeling were found to be more highly expressed at stage 33, including genes related to osteoclast activity, normally associated with removal of bone, a tissue absent in chondrichthyans. These genes are potentially related to loss of mineralization as vertebral elements are incorporated into the synarcual.

Analysis of the middle region of the pharynx in adolescents with different anteroposterior craniofacial skeletal patterns.

ABSTRACTObjective: To assess the volume and morphology of the middle region of the pharynx (MRP) in adolescents with different anteroposterior craniofacial skeletal patterns. Methods: One hundred twenty-six patients (56 male and 70 female), who had cone-beam computed tomography (CBCT) within their records, were selected for this cross-sectional study. Participants were classified, according to their ANB angle value, in Class I (1o ≤ ANB ≤ 3o), Class II (ANB > 3o) and Class III (ANB < 1o). The total volume (tV), minimum axial area (AxMin) and morphology of the MRP and its subdivisions - velopharynx (VP) and oropharynx (OP) - were characterized by CBCT and 3-dimensional image reconstruction software. Intergroup comparisons were performed by ANOVA and Tukey post-hoc tests. Correlations between tV and Axmin with the ANB angle values were tested using linear regression analysis, considering sex as covariable. Results: Statistically significant difference between groups were observed in tV only for the VP region; Class II individuals presented significantly lower tV (6863.75 ± 2627.20 mm3) than Class III subjects (9011.62 ± 3442.56 mm3) (p< 0.05). No significant differences were observed between groups for any other variable assessed, neither in MRP nor in the OP region (p> 0.05). A significant negative correlation was evidenced between tV and Axmin and the ANB angle values; sexual dimorphism was observed for some variables. Conclusions: Class II subjects have smaller tV in the VP region. tV and Axmin tend to decrease in all evaluated regions when the ANB angle values increase.

Correlation of linear dimensions of sella turcica with anteroposterior skeletal jaw relationship of Egyptian subjects using CBCT

The aim of this retrospective study was to find whether there is a correlation between the linear dimensions of the sella turcica and different anteroposterior skeletal growth patterns in an Egyptian population using CBCT. CBCT radiographs of 129 adult patients (60 males, 69 females) were retrieved from the archive of the radiology department of the Faculty of Dentistry, Suez Canal University. They were divided into three groups according to sagittal growth pattern and the sella turcica length, depth and diameter were measured for each case. No statistically significant differences were found between all sella turcica measurements and the anteroposterior jaw relationship. The p-values were 0.087, 0.007 and 0.998 for the diameter, depth and length respectively.

Prevalence of impacted third molars among orthodontic patients in different malocclusions.

The aim of this retrospective study was to investigate the prevalence and pattern of third molar impaction and missing third molars in patients over 18 years in different anteroposterior skeletal patterns among central Indian populations. The study reviewed 357 orthopantomograms of patients attending the Government College of Dentistry, Indore, Madhya Pradesh. Patients were evaluated to determine the prevalence of third molar impaction, angulation, and level of eruption in Class I, Class II, and Class III patients using Winter's classification to determine angulation of third molars and Pell and Gregory classification for level of impaction. Out of 357 patients, 187 (52.3%) were present with at least one impacted teeth. The third molar impaction was most commonly present in Class II malocclusion (60.65%). Overall, the most common angulation of impaction in both genders was the mesioangular (39%), and the most common level of impaction in both arches was Level B. In Class I, Class II and Class III malocclusion vertical angulation was the most common finding in the maxillary arch and mesioangular angulation in the mandibular arch. No significant association was observed between different types of malocclusion and third molar impaction (P > 0.4648). This study found that almost half of the adult patients above 18 years had at least one impacted third molar. The anteroposterior relationship does not have any significant role for the third molar impaction.

Hindbrain induction and patterning during early vertebrate development.

The hindbrain is a key relay hub of the central nervous system (CNS), linking the bilaterally symmetric half-sides of lower and upper CNS centers via an extensive network of neural pathways. Dedicated neural assemblies within the hindbrain control many physiological processes, including respiration, blood pressure, motor coordination and different sensations. During early development, the hindbrain forms metameric segmented units known as rhombomeres along the antero-posterior (AP) axis of the nervous system. These compartmentalized units are highly conserved during vertebrate evolution and act as the template for adult brainstem structure and function. TALE and HOX homeodomain family transcription factors play a key role in the initial induction of the hindbrain and its specification into rhombomeric cell fate identities along the AP axis. Signaling pathways, such as canonical-Wnt, FGF and retinoic acid, play multiple roles to initially induce the hindbrain and regulate Hox gene-family expression to control rhombomeric identity. Additional transcription factors including Krox20, Kreisler and others act both upstream and downstream to Hox genes, modulating their expression and protein activity. In this review, we will examine the earliest embryonic signaling pathways that induce the hindbrain and subsequent rhombomeric segmentation via Hox and other gene expression. We will examine how these signaling pathways and transcription factors interact to activate downstream targets that organize the segmented AP pattern of the embryonic vertebrate hindbrain.

Comparison of condylar size among different anteroposterior and vertical skeletal patterns using cone-beam computed tomography.

To compare condylar size among different anteroposterior and vertical skeletal patterns using cone-beam computed tomography (CBCT). The study included 166 subjects (61 men, mean age: 27.2 ± 7.6 years; 105 women, mean age: 27.4 ± 9.2 years). The anteroposterior skeletal patterns of the subjects were classified into Classes I (-1° ≤ A point-nasion-B point angle [ANB] < 4°), II (ANB ≥ 4°), and III (ANB < -1°). The vertical skeletal patterns were classified into hypodivergent (mandibular plane [MP] ≤ 23°), normodivergent (23° < MP < 30°), and hyperdivergent (MP ≥ 30°) groups. The condylar length, height, and width were examined using CBCT images. Analysis of covariance was used to compare three condylar size measurements among the three anteroposterior groups and the three vertical groups using sex as a covariate. Both left and right sides were examined. Nine groups were further divided according to the anteroposterior and vertical groups, and two-way analysis of covariance (ANCOVA) was applied to estimate the composite effect of skeletal patterns in both directions. Sex as a covariate showed statistical significance in most examinations. The condylar height on both sides had statistically different anteroposterior skeletal patterns ( P < .001). The condylar width on both sides also had statistically different vertical skeletal patterns ( P < .001). After adjusting for sex, the condylar height and width on both sides increased from Class II, Class I, and Class III. The condylar width on both sides increased from the hypodivergent group, the normodivergent group, and the hyperdivergent group. No composite effect of skeletal patterns in both directions was observed. Condylar height and width considerably differed among subjects with different anteroposterior or vertical skeletal patterns. The anteroposterior or vertical skeletal patterns independently affected the condylar size.

De novo neurogenesis in a budding chordate: Co-option of larval anteroposterior patterning genes in a transitory neurogenic organ

During metamorphosis of solitary ascidians, part of the larval tubular nervous system is recruited to form the adult central nervous system (CNS) through neural stem-like cells called ependymal cells. The anteroposterior (AP) gene expression patterning of the larval CNS regionalize the distribution of the ependymal cells, which contains the positional information of the neurons of the adult nervous system.In colonial ascidians, the CNS of asexually developed zooids has the same morphology of the one of the post-metamorphic zooids. However, its development follows a completely different organogenesis that lacks embryogenesis, a larval phase and metamorphosis.In order to describe neurogenesis during asexual development (blastogenesis), we followed the expression of six CNS AP patterning genes conserved in chordates and five neural-related genes to determine neural cell identity in Botryllus schlosseri.We observed that a neurogenesis occurs de novo on each blastogenic cycle starting from a neurogenic transitory structure, the dorsal tube. The dorsal tube partially co-opts the AP patterning of the larval CNS markers, and potentially combine the neurogenesis role and provider of positional clues for neuron patterning. This study shows how a larval developmental module is reused in a direct asexual development in order to generate the same structures.