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Biology Open Jul 2021Early embryogenesis requires tightly controlled temporal and spatial coordination of cellular behavior and signaling. Modulations are achieved at multiple levels, from...
Early embryogenesis requires tightly controlled temporal and spatial coordination of cellular behavior and signaling. Modulations are achieved at multiple levels, from cellular transcription to tissue-scale behavior. Intracellularly, the endolysosomal system emerges as an important regulator at different levels, but in vivo studies are rare. In the frog Xenopus, little is known about the developmental roles of endosomal regulators, or their potential involvement in signaling, especially for late endosomes. Here, we analyzed a hypothesized role of Rab7 in this context, a small GTPase known for its role as a late endosomal regulator. First, rab7 showed strong maternal expression. Following localized zygotic transcript enrichment in the mesodermal ring and neural plate, it was found in tailbud-stage neural ectoderm, notochord, pronephros, eyes and neural crest tissues. Inhibition resulted in strong axis defects caused by a requirement of rab7 for mesodermal patterning and correct gastrulation movements. To test a potential involvement in growth factor signaling, we analyzed early Wnt-dependent processes in the mesoderm. Our results suggest a selective requirement for ligand-induced Wnt activation, implicating a context-dependent role of Rab7.
Topics: Animals; Embryo, Nonmammalian; Embryonic Development; Gastrulation; Gene Expression Regulation, Developmental; Mesoderm; Transcription Factors; Xenopus; Zygote; rab7 GTP-Binding Proteins
PubMed: 34096568
DOI: 10.1242/bio.056887 -
Seminars in Cell & Developmental Biology Nov 2022Gastrulation is a fundamental process during embryonic development, conserved across all multicellular animals [1]. In the majority of metazoans, gastrulation is... (Review)
Review
Gastrulation is a fundamental process during embryonic development, conserved across all multicellular animals [1]. In the majority of metazoans, gastrulation is characterised by large scale morphogenetic remodeling, leading to the conversion of an early pluripotent embryonic cell layer into the three primary 'germ layers': an outer ectoderm, inner endoderm and intervening mesoderm layer. The morphogenesis of these three layers of cells is closely coordinated with cellular diversification, laying the foundation for the generation of the hundreds of distinct specialized cell types in the animal body. The process of gastrulation has for a long time attracted tremendous attention in a broad range of experimental systems ranging from sponges to mice. In humans the process of gastrulation starts approximately 14 days after fertilization and continues for slightly over a week. However our understanding of this important process, as it pertains to human, is limited. Donations of human fetal material at these early stages are exceptionally rare, making it nearly impossible to study human gastrulation directly. Therefore, our understanding of human gastrulation is predominantly derived from animal models such as the mouse [2,3] and from studies of limited collections of fixed whole samples and histological sections of human gastrulae [4-7], some of which date back to over a century ago. More recently we have been gaining valuable molecular insights into human gastrulation using in vitro models of hESCs [8-12] and increasingly, in vitro cultured human and non-human primate embryos [13-16]. However, while methods have been developed to culture human embryos into this stage (and probably beyond), current ethical standards prohibit the culture of human embryos past 14 days again limiting our ability to experimentally probe human gastrulation. This review discusses recent molecular insights from the study of a rare CSĀ 7 human gastrula obtained as a live sample and raises several questions arising from this recent study that it will be interesting to address in the future using emerging models of human gastrulation.
Topics: Animals; Ectoderm; Endoderm; Female; Gastrula; Gastrulation; Humans; Mesoderm; Mice; Pregnancy
PubMed: 35606274
DOI: 10.1016/j.semcdb.2022.05.004 -
WormBook : the Online Review of C.... Jan 2006Early cell lineages and arrangement of blastomeres in C. elegans are similar to the pattern found in Ascaris and other studied nematodes leading to the assumption that... (Review)
Review
Early cell lineages and arrangement of blastomeres in C. elegans are similar to the pattern found in Ascaris and other studied nematodes leading to the assumption that embryonic development shows little variation within the phylum Nematoda. However, analysis of a larger variety of species from various branches of the phylogenetic tree demonstrate that prominent variations in crucial steps of early embryogenesis exist among representatives of this taxon. So far, most of these variations have only been studied on a descriptive level and thus essentially nothing is known about their molecular or genetic basis. Nevertheless, it is obvious that the limited morphological diversity of the freshly hatched juvenile and the uniformity of the basic body plan contrast with the many modifications in the way a worm is generated from the egg cell. This chapter focuses on the initial phase between egg activation and gastrulation and deals with the following aspects: reproduction and diploidy, polarity, cleavage and germ line, cell lineages; cell cycles and maternal contribution, cell-cell communication and cell specification, gastrulation.
Topics: Animals; Cell Communication; Cell Division; Cell Lineage; Diploidy; Gastrulation; Germ Cells; Nematoda
PubMed: 18050475
DOI: 10.1895/wormbook.1.55.1 -
International Journal of Molecular... Jun 2020Early embryonic cells are sensitive to genotoxic stressors such as ionizing radiation. However, sensitivity to these stressors varies depending on the embryonic stage.... (Review)
Review
Early embryonic cells are sensitive to genotoxic stressors such as ionizing radiation. However, sensitivity to these stressors varies depending on the embryonic stage. Recently, the sensitivity and response to ionizing radiation were found to differ during the preimplantation period. The cellular and molecular mechanisms underlying the change during this period are beginning to be elucidated. In this review, we focus on the changes in radio-sensitivity and responses to ionizing radiation during the early developmental stages of the preimplantation (before gastrulation) period in mammals, , and fish. Furthermore, we discuss the underlying cellular and molecular mechanisms and the similarities and differences between species.
Topics: Animals; Apoptosis; Blastocyst; Cell Cycle; DNA Damage; DNA Repair; Gastrulation; Genome; Humans; Mice; Mutagens; Radiation Tolerance; Radiation, Ionizing; Xenopus laevis
PubMed: 32492918
DOI: 10.3390/ijms21113975 -
Developmental Biology Jun 2021Recent advances in synthetic human embryology has provided a previously inexistent molecular portrait of human development. Models of synthetic human embryonic tissues... (Review)
Review
Recent advances in synthetic human embryology has provided a previously inexistent molecular portrait of human development. Models of synthetic human embryonic tissues capitalize on the self-organizing capabilities of human embryonic stem cells when they are cultured on biomimetic conditions that simulate in vivo human development. In this Review, we discuss these models and how they have shed light on the early stages of human development including amniotic sac development, gastrulation and neurulation. We discuss the mechanisms underlying the molecular logic of embryonic tissue self-organization that have been dissected using synthetic models of human embryology and explore future challenges in the field. Geared with technological advances in bioengineering, high resolution gene expression and imaging tools, these models are set to transform our understanding of the mechanistic basis of embryonic tissue self-organization during human development and how they may go awry in disease.
Topics: Amnion; Ectoderm; Embryo Implantation; Embryonic Development; Embryonic Stem Cells; Gastrulation; Humans; Neurulation; Synthetic Biology
PubMed: 33476596
DOI: 10.1016/j.ydbio.2021.01.004 -
Cell Aug 2022Mice deficient for all ten-eleven translocation (TET) genes exhibit early gastrulation lethality. However, separating cause and effect in such embryonic failure is...
Mice deficient for all ten-eleven translocation (TET) genes exhibit early gastrulation lethality. However, separating cause and effect in such embryonic failure is challenging. To isolate cell-autonomous effects of TET loss, we used temporal single-cell atlases from embryos with partial or complete mutant contributions. Strikingly, when developing within a wild-type embryo, Tet-mutant cells retain near-complete differentiation potential, whereas embryos solely comprising mutant cells are defective in epiblast to ectoderm transition with degenerated mesoderm potential. We map de-repressions of early epiblast factors (e.g., Dppa4 and Gdf3) and failure to activate multiple signaling from nascent mesoderm (Lefty, FGF, and Notch) as likely cell-intrinsic drivers of TET loss phenotypes. We further suggest loss of enhancer demethylation as the underlying mechanism. Collectively, our work demonstrates an unbiased approach for defining intrinsic and extrinsic embryonic gene function based on temporal differentiation atlases and disentangles the intracellular effects of the demethylation machinery from its broader tissue-level ramifications.
Topics: Animals; Cell Differentiation; Embryo, Mammalian; Gastrulation; Gene Expression Regulation, Developmental; Mesoderm; Mice; Nuclear Proteins; Signal Transduction
PubMed: 35908548
DOI: 10.1016/j.cell.2022.06.049 -
Cold Spring Harbor Perspectives in... Jul 2015The field of miRNA biology is relatively young, but its impact on our understanding of the regulation of a wide array of cell functions is far-reaching. The importance... (Review)
Review
The field of miRNA biology is relatively young, but its impact on our understanding of the regulation of a wide array of cell functions is far-reaching. The importance of miRNAs in development has become nearly ubiquitous, with miRNAs contributing to development of most cells and organs. Although miRNAs are clearly interwoven into known regulatory networks that control cell development, the specific modalities by which they intersect are often quite distinct and cleverly achieved. The frequently emerging theme of feed-back and feed-forward loops to either counterbalance or reinforce the gene programs that they influence is a common thread. Many of these examples of miRNAs as developmental regulators are presently found in organs with different miRNAs and targets, whereas novel, unexpected themes emerge in the context of mouse development as we learn more about this rapidly developing area of biology.
Topics: Animals; Bone Development; Cell Differentiation; Gastrulation; Gene Expression Regulation, Developmental; Hematopoiesis; Mice; MicroRNAs; Models, Genetic; Muscle Development; Nervous System; Signal Transduction
PubMed: 26134312
DOI: 10.1101/cshperspect.a008144 -
Methods in Molecular Biology (Clifton,... 2022Apical constriction refers to the active, actomyosin-driven process that reduces apical cell surface area in epithelial cells. Apical constriction is utilized in...
Apical constriction refers to the active, actomyosin-driven process that reduces apical cell surface area in epithelial cells. Apical constriction is utilized in epithelial morphogenesis during embryonic development in multiple contexts, such as gastrulation, neural tube closure, and organogenesis. Defects in apical constriction can result in congenital birth defects, yet our understanding of the molecular control of apical constriction is relatively limited. To uncover new genetic regulators of apical constriction and gain mechanistic insight into the cell biology of this process, we need reliable assay systems that allow real-time observation and quantification of apical constriction as it occurs and permit gain- and loss-of-function analyses to explore gene function and interaction during apical constriction. In this chapter, we describe using the early Xenopus embryo as an assay system to investigate molecular mechanisms involved in apical constriction during both gastrulation and neurulation.
Topics: Animals; Constriction; Gastrulation; Morphogenesis; Neurulation; Xenopus laevis
PubMed: 35147955
DOI: 10.1007/978-1-0716-2035-9_24 -
ELife May 2022Cells sense and integrate external information from diverse sources that include mechanical cues. Shaping of tissues during development may thus require coordination...
Cells sense and integrate external information from diverse sources that include mechanical cues. Shaping of tissues during development may thus require coordination between mechanical forces from morphogenesis and cell-cell signalling to confer appropriate changes in gene expression. By live-imaging Notch-induced transcription in real time, we have discovered that morphogenetic movements during gastrulation bring about an increase in activity-levels of a Notch-responsive enhancer. Mutations that disrupt the timing of gastrulation resulted in concomitant delays in transcription up-regulation that correlated with the start of mesoderm invagination. As a similar gastrulation-induced effect was detected when transcription was elicited by the intracellular domain NICD, it cannot be attributed to forces exerted on Notch receptor activation. A Notch-independent enhancer also exhibited a modest gastrulation-induced activity increase in the same stripe of cells. Together, these observations argue that gastrulation-associated forces act on the nucleus to modulate transcription levels. This regulation was uncoupled when the complex linking the nucleoskeleton and cytoskeleton (LINC) was disrupted, indicating a likely conduit. We propose that the coupling between tissue-level mechanics, arising from gastrulation, and enhancer activity represents a general mechanism for ensuring correct tissue specification during development and that Notch-dependent enhancers are highly sensitive to this regulation.
Topics: Animals; Drosophila; Gastrulation; Gene Expression Regulation, Developmental; Mesoderm; Morphogenesis; Receptors, Notch; Signal Transduction
PubMed: 35583918
DOI: 10.7554/eLife.73656 -
Nature Communications Sep 2023Understanding of the molecular drivers of lineage diversification and tissue patterning during primary germ layer development requires in-depth knowledge of the dynamic...
Understanding of the molecular drivers of lineage diversification and tissue patterning during primary germ layer development requires in-depth knowledge of the dynamic molecular trajectories of cell lineages across a series of developmental stages of gastrulation. Through computational modeling, we constructed at single-cell resolution, a spatio-temporal transcriptome of cell populations in the germ-layers of gastrula-stage mouse embryos. This molecular atlas enables the inference of molecular network activity underpinning the specification and differentiation of the germ-layer tissue lineages. Heterogeneity analysis of cellular composition at defined positions in the epiblast revealed progressive diversification of cell types. The single-cell transcriptome revealed an enhanced BMP signaling activity in the right-side mesoderm of late-gastrulation embryo. Perturbation of asymmetric BMP signaling activity at late gastrulation led to randomization of left-right molecular asymmetry in the lateral mesoderm of early-somite-stage embryo. These findings indicate the asymmetric BMP activity during gastrulation may be critical for the symmetry breaking process.
Topics: Animals; Mice; Gastrulation; Functional Laterality; Gastrula; Germ Layers; Mesoderm
PubMed: 37709743
DOI: 10.1038/s41467-023-41482-5