-
Journal of Korean Neurosurgical Society May 2021It has been recognised for over a century that the events of gastrulation are fundamental in determining, not only the development of the neuraxis but the organisation...
It has been recognised for over a century that the events of gastrulation are fundamental in determining, not only the development of the neuraxis but the organisation of the entire primitive embryo. Until recently our understanding of gastrulation was based on detailed histological analysis in animal models and relatively rare human tissue preparations from aborted fetuses. Such studies resulted in a model of gastrulation that neurosurgeons have subsequently used as a means of trying to explain some of the congenital anomalies of caudal spinal cord and vertebral development that present in paediatric neurosurgical practice. Recent advances in developmental biology, in particular cellular biology and molecular genetics have offered new insights into very early development. Understanding the processes that underlie cellular interactions, gene expression and activation/inhibition of signalling pathways has changed the way embryologists view gastrulation and this has led to a shift in emphasis from the 'descriptive and morphological' to the 'mechanistic and functional'. Unfortunately, thus far it has proved difficult to translate this improved knowledge of normal development, typically derived from non-human models, into an understanding of the mechanisms underlying human malformations such as the spinal dysraphisms and anomalies of caudal development. A paediatric neurosurgeons perspective of current concepts in gastrulation is presented along with a critical review of the current hypotheses of human malformations that have been attributed to disorders of this stage of embryogenesis.
PubMed: 33321561
DOI: 10.3340/jkns.2020.0125 -
Developmental Cell Jan 2021Somite formation is foundational to creating the vertebrate segmental body plan. Here, we describe three transcriptional trajectories toward somite formation in the...
Somite formation is foundational to creating the vertebrate segmental body plan. Here, we describe three transcriptional trajectories toward somite formation in the early mouse embryo. Precursors of the anterior-most somites ingress through the primitive streak before E7 and migrate anteriorly by E7.5, while a second wave of more posterior somites develops in the vicinity of the streak. Finally, neuromesodermal progenitors (NMPs) are set aside for subsequent trunk somitogenesis. Single-cell profiling of T chimeric embryos shows that the anterior somites develop in the absence of T and suggests a cell-autonomous function of T as a gatekeeper between paraxial mesoderm production and the building of the NMP pool. Moreover, we identify putative regulators of early T-independent somites and challenge the T-Sox2 cross-antagonism model in early NMPs. Our study highlights the concept of molecular flexibility during early cell-type specification, with broad relevance for pluripotent stem cell differentiation and disease modeling.
Topics: Animals; Body Patterning; Cell Differentiation; Cell Line; Chimera; Embryo, Mammalian; Female; Fetal Proteins; Gene Expression Profiling; Gene Expression Regulation, Developmental; Germ Cells; Heterozygote; Male; Mesoderm; Mice; Mice, Inbred C57BL; SOXB1 Transcription Factors; Single-Cell Analysis; Somites; T-Box Domain Proteins; Transcriptome
PubMed: 33308481
DOI: 10.1016/j.devcel.2020.11.013 -
Nature Communications Nov 2020Coordinated directional migration of cells in the mesoderm layer of the early embryo is essential for organization of the body plan. Here we show that mesoderm...
Coordinated directional migration of cells in the mesoderm layer of the early embryo is essential for organization of the body plan. Here we show that mesoderm organization in mouse embryos depends on β-Pix (Arhgef7), a guanine nucleotide exchange factor for Rac1 and Cdc42. As early as E7.5, β-Pix mutants have an abnormally thick mesoderm layer; later, paraxial mesoderm fails to organize into somites. To define the mechanism of action of β-Pix in vivo, we optimize single-cell live-embryo imaging, cell tracking, and volumetric analysis of individual and groups of mesoderm cells. Use of these methods shows that wild-type cells move in the same direction as their neighbors, whereas adjacent β-Pix mutant cells move in random directions. Wild-type mesoderm cells have long polarized filopodia-like protrusions, which are absent in β-Pix mutants. The data indicate that β-Pix-dependent cellular protrusions drive and coordinate collective migration of the mesoderm in vivo.
Topics: Animals; Cell Movement; Cell Polarity; Cell Surface Extensions; Embryo, Mammalian; Epithelium; Female; Gastrulation; Green Fluorescent Proteins; Imaging, Three-Dimensional; Male; Mesoderm; Mice, Inbred C57BL; Morphogenesis; Mutation; Phenotype; Primitive Streak; Rheology; Rho Guanine Nucleotide Exchange Factors
PubMed: 33247143
DOI: 10.1038/s41467-020-19889-1 -
Anatomical Record (Hoboken, N.J. : 2007) Jul 2021The objective of this study was to characterize the external morphology of Salvator meriane embryos in different stages of embryonic development and establish a...
The objective of this study was to characterize the external morphology of Salvator meriane embryos in different stages of embryonic development and establish a relationship with the ultrastructure of the shell from oviductal transit to hatching. A total of 120 embryos were analyzed to describe their external morphology, and 78 eggs were used for the analysis of the shell. For embryonic development, the series was established according to the total length of the body. We established 40 embryonic stages from the primitive streak. In the early stages, the external morphological features are the C-shaped body, the maxillary, and mandibular fusion processes with the frontal process and the fusion of the forelimb with the digital plate. In the middle stages, the eyelid appears, and there are claws on the toes, cornification of fingers, and the onset of pigmentation. The last stage of embryonic development is characterized by the beginning of the formation of the scales, appear the toenails, and finalize the entire pigmentation. Regarding the relationship that exists with the ultrastructure of the egg during development, it was possible to observe a marked change in the composition of the shell and well-marked compaction during embryonic development, which may be related to the transport of calcium during embryonic ossification. Our results allowed us to show the complete sequence of embryonic development, determining the laying stage for this species. It was possible to establish a relationship with the ultrastructure of the eggshell from the oviductal transit to the moment of hatching.
Topics: Animals; Egg Shell; Embryonic Development; Lizards
PubMed: 33099895
DOI: 10.1002/ar.24546 -
PloS One 2020Hybrid incompatibility, such as sterility and inviability, prevents gene flow between closely-related populations as a reproductive isolation barrier. F1 hybrids between...
Hybrid incompatibility, such as sterility and inviability, prevents gene flow between closely-related populations as a reproductive isolation barrier. F1 hybrids between chickens and Japanese quail (hereafter, referred to as quail), exhibit a high frequency of developmental arrest at the preprimitive streak stage. To investigate the molecular basis of the developmental arrest at the preprimitive streak stage in chicken-quail F1 hybrid embryos, we investigated chromosomal abnormalities in the hybrid embryos using molecular cytogenetic analysis. In addition, we quantified gene expression in parental species and chicken- and quail-derived allele-specific expression in the hybrids at the early blastoderm and preprimitive streak stages by mRNA sequencing. Subsequently, we compared the directions of change in gene expression, including upregulation, downregulation, or no change, from the early blastoderm stage to the preprimitive streak stage between parental species and their hybrids. Chromosome analysis revealed that the cells of the hybrid embryos contained a fifty-fifty mixture of parental chromosomes, and numerical chromosomal abnormalities were hardly observed in the hybrid cells. Gene expression analysis revealed that a part of the genes that were upregulated from the early blastoderm stage to the preprimitive streak stage in both parental species exhibited no upregulation of both chicken- and quail-derived alleles in the hybrids. GO term enrichment analysis revealed that these misregulated genes are involved in various biological processes, including ribosome-mediated protein synthesis and cell proliferation. Furthermore, the misregulated genes included genes involved in early embryonic development, such as primitive streak formation and gastrulation. These results suggest that numerical chromosomal abnormalities due to a segregation failure does not cause the lethality of chicken-quail hybrid embryos, and that the downregulated expression of the genes that are involved in various biological processes, including translation and primitive streak formation, mainly causes the developmental arrest at the preprimitive streak stage in the hybrids.
Topics: Animals; Blastoderm; Chickens; Chromosome Aberrations; Hybridization, Genetic; Quail; Transcriptome
PubMed: 33044996
DOI: 10.1371/journal.pone.0240183 -
EMBO Reports Nov 2020At gastrulation, a subpopulation of epiblast cells constitutes a transient posteriorly located structure called the primitive streak, where cells that undergo...
At gastrulation, a subpopulation of epiblast cells constitutes a transient posteriorly located structure called the primitive streak, where cells that undergo epithelial-mesenchymal transition make up the mesoderm and endoderm lineages. Mouse embryo epiblast cells were labelled ubiquitously or in a mosaic fashion. Cell shape, packing, organization and division were recorded through live imaging during primitive streak formation. Posterior epiblast displays a higher frequency of rosettes, some of which associate with a central cell undergoing mitosis. Cells at the primitive streak, in particular delaminating cells, undergo mitosis more frequently than other epiblast cells. In pseudostratified epithelia, mitosis takes place at the apical side of the epithelium. However, mitosis is not restricted to the apical side of the epiblast, particularly on its posterior side. Non-apical mitosis occurs specifically in the streak even when ectopically located. Posterior non-apical mitosis results in one or two daughter cells leaving the epiblast layer. Cell rearrangement associated with mitotic cell rounding in posterior epiblast, in particular when non-apical, might thus facilitate cell ingression and transition to a mesenchymal phenotype.
Topics: Animals; Epithelial-Mesenchymal Transition; Gastrulation; Germ Layers; Mesoderm; Mice; Mitosis
PubMed: 33016470
DOI: 10.15252/embr.202050944 -
Biology Open Aug 2020The mouse T-box transcription factors T and Tbx6 are co-expressed in the primitive streak and have unique domains of expression; T is expressed in the notochord, while...
The mouse T-box transcription factors T and Tbx6 are co-expressed in the primitive streak and have unique domains of expression; T is expressed in the notochord, while Tbx6 is expressed in the presomitic mesoderm. T-box factors are related through a shared DNA binding domain, the T-domain, and can therefore bind to similar DNA sequences at least We investigated the functional similarities and differences of T and Tbx6 DNA binding and transcriptional activity and their interaction genetically We show that at one target, , the T-domains of T and Tbx6 have different affinities for the binding sites present in the mesoderm enhancer. We further show using assays that T and Tbx6 differentially affect transcription with Tbx6 activating expression tenfold higher than T, that T and Tbx6 can compete at target gene enhancers, and that this competition requires a functional DNA binding domain. Next, we addressed whether T and Tbx6 can compete First, we generated embryos that express Tbx6 at greater than wild-type levels embryos and show that these embryos have short tails, resembling the heterozygous phenotype. Next, using the dominant-negative allele, we show that embryos share similarities with embryos homozygous for the hypomorphic allele , specifically fusions of several ribs and malformation of some vertebrae. Finally, we tested whether Tbx6 can functionally replace T using a knockin approach, which resulted in severe null-like phenotypes in chimeric embryos generated with ES cells heterozygous for a knockin at the locus. Altogether, our results of differences in affinity for DNA binding sites and transcriptional activity for T and Tbx6 provide a potential mechanism for the failure of Tbx6 to functionally replace T and possible competition phenotypes .
Topics: Alleles; Animals; Base Sequence; Binding Sites; Embryo, Mammalian; Embryonic Development; Enhancer Elements, Genetic; Fetal Proteins; Gene Expression Regulation, Developmental; HEK293 Cells; Humans; Luciferases; Mice; Phenotype; Protein Domains; T-Box Domain Proteins; Transcription, Genetic; Up-Regulation
PubMed: 32855167
DOI: 10.1242/bio.054692 -
Diagnostic Pathology Jul 2020Patients with 46, XY disorder of sex development (DSD) are predisposed to the development of gonadal tumors, particularly germ cell tumors and gonadoblastoma. However,... (Review)
Review
BACKGROUND
Patients with 46, XY disorder of sex development (DSD) are predisposed to the development of gonadal tumors, particularly germ cell tumors and gonadoblastoma. However, to the best of our knowledge, there are no publications in the existing literature that refer to the coexistence of 46, XY DSD and serous tumors in the ovary.
CASE PRESENTATION
Here, we report the case of a 23-year-old female (social gender) patient with 46, XY DSD presenting with primary amenorrhea. Imageology revealed a huge mass in the left adnexa. Subsequent pathological analysis revealed a serous borderline tumor of the ovary.
CONCLUSION
Gonadal tumors of patients with 46, XY DSD are not necessarily malignant tumors and can coexist with borderline tumors with primitive corded gonads. The coexistence of DSD and serous borderline tumors is rare. Clearly, an early and accurate diagnosis plays an important role in the treatment of these patients. Although there may not be a clear correlation between the two lesions, it is vital that we specifically analyze the mechanisms involved so that we can determine whether patients with DSD are associated with an increase of developing serous borderline tumors of the gonad.
Topics: Cystadenoma, Serous; Female; Gonadoblastoma; Humans; Neoplasms, Germ Cell and Embryonal; Ovarian Neoplasms; Ovary; Sex Chromosome Aberrations; Sexual Development; Young Adult
PubMed: 32703224
DOI: 10.1186/s13000-020-01010-1 -
ELife Jun 2020Formation of the vertebrate postcranial body axis follows two sequential but distinct phases. The first phase generates pre-sacral structures (the so-called primary...
Formation of the vertebrate postcranial body axis follows two sequential but distinct phases. The first phase generates pre-sacral structures (the so-called primary body) through the activity of the primitive streak on axial progenitors within the epiblast. The embryo then switches to generate the secondary body (post-sacral structures), which depends on axial progenitors in the tail bud. Here we show that the mammalian tail bud is generated through an independent functional developmental module, concurrent but functionally different from that generating the primary body. This module is triggered by convergent Tgfbr1 and Snai1 activities that promote an incomplete epithelial to mesenchymal transition on a subset of epiblast axial progenitors. This EMT is functionally different from that coordinated by the primitive streak, as it does not lead to mesodermal differentiation but brings axial progenitors into a transitory state, keeping their progenitor activity to drive further axial body extension.
Topics: Animals; Body Patterning; Embryo, Mammalian; Epithelial-Mesenchymal Transition; Mesoderm; Mice; Mice, Transgenic; Receptor, Transforming Growth Factor-beta Type I; Snail Family Transcription Factors; Tail
PubMed: 32597756
DOI: 10.7554/eLife.56615 -
Mechanisms of Development Sep 2020Gastrulation consists in the dramatic reorganisation of the epiblast, a one-cell thick epithelial sheet, into a multilayered embryo. In chick, the formation of the... (Review)
Review
Gastrulation consists in the dramatic reorganisation of the epiblast, a one-cell thick epithelial sheet, into a multilayered embryo. In chick, the formation of the internal layers requires the generation of a macroscopic convection-like flow, which involves up to 50,000 epithelial cells in the epiblast. These cell movements locate the mesendoderm precursors into the midline of the epiblast to form the primitive streak. There they acquire a mesenchymal phenotype, ingress into the embryo and migrate outward to populate the inner embryonic layers. This review covers what is currently understood about how cell behaviours ultimately cause these morphogenetic events and how they are regulated. We discuss 1) how the biochemical patterning of the embryo before gastrulation creates compartments of differential cell behaviours, 2) how the global epithelial flows arise from the coordinated actions of individual cells, 3) how the cells delaminate individually from the epiblast during the ingression, and 4) how cells move after the ingression following stereotypical migration routes. We conclude by exploring new technical advances that will facilitate future research in the chick model system.
Topics: Animals; Chick Embryo; Chickens; Gastrula; Gastrulation; Germ Layers; Mesoderm; Morphogenesis
PubMed: 32562871
DOI: 10.1016/j.mod.2020.103624