Cell Fate Decisions During Preimplantation Mammalian Development

A critical point in mammalian development is when the early embryo implants into its mother's uterus. This event has historically been difficult to study due to the fact that it occurs within the maternal tissue and therefore is hidden from view. In this review, we discuss how the mouse embryo is prepared for implantation and the molecular mechanisms involved in directing and coordinating this crucial event. Prior to implantation, the cells of the embryo are specified as precursors of future embryonic and extra-embryonic lineages. These preimplantation cell fate decisions rely on a combination of factors including cell polarity, position and cell–cell signalling and are influenced by the heterogeneity between early embryo cells. At the point of implantation, signalling events between the embryo and mother, and between the embryonic and extraembryonic compartments of the embryo itself, orchestrate a total reorganization of the embryo, coupled with a burst of cell proliferation. New developments in embryo culture and imaging techniques have recently revealed the growth and morphogenesis of the embryo at the time of implantation, leading to a new model for the blastocyst to egg cylinder transition. In this model, pluripotent cells that will give rise to the fetus self-organize into a polarized three-dimensional rosette-like structure that initiates egg cylinder formation.

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Super-Enhancers and CTCF in Early Embryonic Cell Fate Decisions

Frontiers in Cell and Developmental Biology ◽

10.3389/fcell.2021.653669 ◽

2021 ◽

Vol 9 ◽

Author(s):

Puja Agrawal ◽

Sridhar Rao

Keyword(s):

Gene Expression ◽

Cell Fate ◽

Critical Role ◽

Regulatory Elements ◽

Specific Gene ◽

Cell Type ◽

Mammalian Development ◽

Cell Fate Decisions ◽

Cell Type Specific ◽

Early Mammalian Development

Cell fate decisions are the backbone of many developmental and disease processes. In early mammalian development, precise gene expression changes underly the rapid division of a single cell that leads to the embryo and are critically dependent on autonomous cell changes in gene expression. To understand how these lineage specifications events are mediated, scientists have had to look past protein coding genes to the cis regulatory elements (CREs), including enhancers and insulators, that modulate gene expression. One class of enhancers, termed super-enhancers, is highly active and cell-type specific, implying their critical role in modulating cell-type specific gene expression. Deletion or mutations within these CREs adversely affect gene expression and development and can cause disease. In this mini-review we discuss recent studies describing the potential roles of two CREs, enhancers and binding sites for CTCF, in early mammalian development.

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Tracing the Transitions from Pluripotency to Germ Cell Fate with CRISPR Screening

10.1101/269811 ◽

2018 ◽

Cited By ~ 1

Author(s):

Jamie A. Hackett ◽

Yun Huang ◽

Ufuk Günesdogan ◽

Kristjan Holm-Gretarsson ◽

Toshihiro Kobayashi ◽

...

Keyword(s):

Germ Cell ◽

Cell Fate ◽

Regulatory Networks ◽

Primordial Germ Cells ◽

Mammalian Development ◽

Reporter System ◽

Cell Fate Decisions ◽

Founding Population ◽

Gene Regulatory ◽

Early Mammalian Development

ABSTRACTEarly mammalian development entails a series of cell fate transitions that includes transit through naïve pluripotency to post-implantation epiblast. This subsequently gives rise to primordial germ cells (PGC), the founding population of the germline lineage. To investigate the gene regulatory networks that control these critical cell fate decisions, we developed a compound-reporter system to track cellular identity in a model of PGC specification (PGC-like cells; PGCLC), and coupled it with unbiased genome-wide CRISPR screening. This enabled identification of key genes both for exit from pluripotency and for acquisition of PGC fate, with further characterisation revealing a central role for the transcription factors Nr5a2 and Zfp296 in germline ontogeny. Abrogation of these genes results in significantly impaired PGCLC development due to widespread activation (Nr5a2−/−) or inhibition (Zfp296−/−) of WNT pathway components. This leads to aberrant upregulation of the somatic programme or failure to appropriately activate germline genes in PGCLC, respectively, and consequently loss of germ cell identity. Overall our study places Zfp296 and Nr5a2 as key components of an expanded PGC gene regulatory network, and outlines a transferable strategy for identifying critical regulators of complex cell fate transitions.

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A homolog of Drosophila Notch expressed during mammalian development

Development ◽

10.1242/dev.113.1.199 ◽

1991 ◽

Vol 113 (1) ◽

pp. 199-205 ◽

Cited By ~ 19

Author(s):

G. Weinmaster ◽

V.J. Roberts ◽

G. Lemke

Keyword(s):

Cell Fate ◽

In Situ Hybridisation ◽

Hair Follicles ◽

Cdna Clones ◽

Mammalian Development ◽

Cell Fate Decisions ◽

Invertebrate Development ◽

Epidermal Growth ◽

Local Cell ◽

Tooth Buds

Drosophila Notch and the related Caenorhabditis elegans proteins lin-12 and glp-1 function as mediators of local cell-cell interactions required for cell-fate decisions during invertebrate development. To investigate the possibility that similar proteins play determinative roles during mammalian development, we isolated cDNA clones encoding rat Notch. The deduced amino acid sequence of this protein contains 36 epidermal growth factor (EGF)-like repeats, and is remarkably similar in both its extracellular and cytoplasmic domains to the sequence of Xenopus Xotch and Drosophila Notch. In the developing central nervous system, in situ hybridisation analyses revealed that Notch transcripts were dramatically restricted to the ventricular proliferative zones of embryonic neuroepithelia. Notch was also strongly expressed during development of non-neural tissues, such as hair follicles and tooth buds, whose correct differentiation requires epithelial-mesenchymal interactions. These data support the hypothesis that Notch plays an essential role in mammalian development and pattern formation that closely parallels its role in the development of invertebrates.

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Computational models for the dynamics of early mouse embryogenesis

The International Journal of Developmental Biology ◽

10.1387/ijdb.180418gd ◽

2019 ◽

Vol 63 (3-4-5) ◽

pp. 131-142 ◽

Cited By ~ 4

Author(s):

Alen Tosenberger ◽

Didier Gonze ◽

Claire Chazaud ◽

Geneviève Dupont

Keyword(s):

Cell Fate ◽

Computational Models ◽

Computational Modelling ◽

Great Level ◽

Primitive Endoderm ◽

Mammalian Development ◽

Cell Fate Decisions ◽

Transcriptomic Data ◽

Regulatory Processes ◽

Early Mouse

Early embryonic development, from the zygote to the blastocyst, is a paradigm of a dynamic, self-organised process. It involves gene expression, mechanical interactions between cells, cell division and inter- and intracellular signalling. Imaging and transcriptomic data have significantly improved our understanding of early embryogenesis in mammals. However, they also reveal a great level of complexity. How the genetic, mechanical, and regulatory processes interact to ensure reproducible development is thus much investigated by computational modelling, which allows a dissection of the mechanisms controlling cell fate decisions. In this review, we discuss the main types of modelling approaches that have been used to investigate the dynamics of preimplantation mammalian development. We also discuss the insights provided by modelling into our understanding of the specification processes leading to the three types of cells in the embryo 4.5 days after fertilization: the trophectoderm, the epiblast and the primitive endoderm.

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Autophagy and mammalian development

Biochemical Society Transactions ◽

10.1042/bst20130185 ◽

2013 ◽

Vol 41 (6) ◽

pp. 1489-1494 ◽

Cited By ~ 28

Author(s):

Xiaoting Wu ◽

Hyeran Won ◽

David C. Rubinsztein

Keyword(s):

Growth Factor ◽

Cell Fate ◽

Transforming Growth Factor ◽

Gene Knockout ◽

Transforming Growth Factor Β ◽

Degradation Pathway ◽

Mammalian Development ◽

Cell Fate Decisions ◽

Gene Knockout Mice ◽

Differentiation And Proliferation

Autophagy is a highly conserved cytoplasmic degradation pathway that has an impact on many physiological and disease states, including immunity, tumorigenesis and neurodegeneration. Recent studies suggest that autophagy may also have important functions in embryogenesis and development. Many autophagy gene-knockout mice have embryonic lethality at different stages of development. Furthermore, interactions of autophagy with crucial developmental pathways such as Wnt, Shh (Sonic Hedgehog), TGFβ (transforming growth factor β) and FGF (fibroblast growth factor) have been reported. This suggests that autophagy may regulate cell fate decisions, such as differentiation and proliferation. In the present article, we discuss how mammalian autophagy may affect phenotypes associated with development.

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