Preimplantation development of the mammalian embryo and its regulation by growth factors

AbstractDuring the first days of mammalian development, the embryo forms the blastocyst, the structure responsible for implanting the mammalian embryo. Consisting of an epithelium enveloping the pluripotent inner cell mass and a fluid-filled lumen, the blastocyst results from a series of cleavages divisions, morphogenetic movements and lineage specification. Recent studies identified the essential role of actomyosin contractility in driving the morphogenesis, fate specification and cytokinesis leading to the formation of the blastocyst. However, the preimplantation development of contractility mutants has not been characterized. Here, we generated single and double maternal-zygotic mutants of non-muscle myosin-II heavy chains (NMHC) to characterize them using multiscale imaging. We find that Myh9 (NMHC II-A) is the major NMHC during preimplantation development as its maternal-zygotic loss causes failed cytokinesis, increased duration of the cell cycle, weaker embryo compaction and reduced differentiation, whereas Myh10 (NMHC II-B) maternal-zygotic loss is much less severe. Double maternal-zygotic mutants for Myh9 and Myh10 show a much stronger phenotype, failing most attempts of cytokinesis. We find that morphogenesis and fate specification are affected but nevertheless carry on in a timely fashion, regardless of the impact of the mutations on cell number. Strikingly, even when all cell divisions fail, the resulting single-celled embryo can initiate trophectoderm differentiation and lumen formation by accumulating fluid in increasingly large vacuoles. Therefore, contractility mutants reveal that fluid accumulation is a cell-autonomous process and that the preimplantation program carries on independently of successful cell division.

Download Full-text

The role of the insulin-like growth factors in preimplantation development

BJOG An International Journal of Obstetrics & Gynaecology ◽

10.1111/j.1471-0528.1998.tb09981_6.x ◽

1998 ◽

Vol 105 (11) ◽

pp. 1221-1221

Author(s):

AD Lighten ◽

GE Moore ◽

RML Winston ◽

K Hardy

Keyword(s):

Growth Factors ◽

Preimplantation Development ◽

Insulin Like Growth Factors

Download Full-text

Multiscale analysis of single and double maternal-zygotic Myh9 and Myh10 mutants during mouse preimplantation development

eLife ◽

10.7554/elife.68536 ◽

2021 ◽

Vol 10 ◽

Author(s):

Markus Frederik Schliffka ◽

Anna-Francesca Tortorelli ◽

Özge Özgüç ◽

Ludmilla de Plater ◽

Oliver Polzer ◽

...

Keyword(s):

Inner Cell Mass ◽

Cell Mass ◽

Cell Number ◽

Preimplantation Development ◽

Mammalian Development ◽

Mammalian Embryo ◽

Fate Specification ◽

Heavy Chains ◽

A Cell ◽

The Impact

During the first days of mammalian development, the embryo forms the blastocyst, the structure responsible for implanting the mammalian embryo. Consisting of an epithelium enveloping the pluripotent inner cell mass and a fluid-filled lumen, the blastocyst results from a series of cleavages divisions, morphogenetic movements and lineage specification. Recent studies identified the essential role of actomyosin contractility in driving the cytokinesis, morphogenesis and fate specification leading to the formation of the blastocyst. However, the preimplantation development of contractility mutants has not been characterized. Here, we generated single and double maternal-zygotic mutants of non-muscle myosin II heavy chains (NMHC) to characterize them with multiscale imaging. We find that Myh9 (NMHC II-A) is the major NMHC during preimplantation development as its maternal-zygotic loss causes failed cytokinesis, increased duration of the cell cycle, weaker embryo compaction and reduced differentiation, whereas Myh10 (NMHC II-B) maternal-zygotic loss is much less severe. Double maternal-zygotic mutants for Myh9 and Myh10 show a much stronger phenotype, failing most attempts of cytokinesis. We find that morphogenesis and fate specification are affected but nevertheless carry on in a timely fashion, regardless of the impact of the mutations on cell number. Strikingly, even when all cell divisions fail, the resulting single-celled embryo can initiate trophectoderm differentiation and lumen formation by accumulating fluid in increasingly large vacuoles. Therefore, contractility mutants reveal that fluid accumulation is a cell-autonomous process and that the preimplantation program carries on independently of successful cell division.

Download Full-text

IVEN: A quantitative tool to describe 3D cell position and neighbourhood reveals architectural changes in FGF4-treated preimplantation embryos

PLoS Biology ◽

10.1371/journal.pbio.3001345 ◽

2021 ◽

Vol 19 (7) ◽

pp. e3001345

Author(s):

Jessica E. Forsyth ◽

Ali H. Al-Anbaki ◽

Roberto de la Fuente ◽

Nikkinder Modare ◽

Diego Perez-Cortes ◽

...

Keyword(s):

Spatial Relations ◽

Preimplantation Development ◽

Preimplantation Embryos ◽

Mammalian Development ◽

Successful Development ◽

Successful Pregnancy ◽

Mammalian Embryo ◽

Cell Position ◽

Different Populations ◽

Quantitative Tool

Architectural changes at the cellular and organism level are integral and necessary to successful development and growth. During mammalian preimplantation development, cells reduce in size and the architecture of the embryo changes significantly. Such changes must be coordinated correctly to ensure continued development of the embryo and, ultimately, a successful pregnancy. However, the nature of such transformations is poorly defined during mammalian preimplantation development. In order to quantitatively describe changes in cell environment and organism architecture, we designed Internal Versus External Neighbourhood (IVEN). IVEN is a user-interactive, open-source pipeline that classifies cells into different populations based on their position and quantifies the number of neighbours of every cell within a dataset in a 3D environment. Through IVEN-driven analyses, we show how transformations in cell environment, defined here as changes in cell neighbourhood, are related to changes in embryo geometry and major developmental events during preimplantation mammalian development. Moreover, we demonstrate that modulation of the FGF pathway alters spatial relations of inner cells and neighbourhood distributions, leading to overall changes in embryo architecture. In conjunction with IVEN-driven analyses, we uncover differences in the dynamic of cell size changes over the preimplantation period and determine that cells within the mammalian embryo initiate growth phase only at the time of implantation.

Download Full-text

Interleukin Gene Expression in Mouse Preimplantation Development

Developmental Immunology ◽

10.1155/1995/26830 ◽

1995 ◽

Vol 4 (3) ◽

pp. 169-179 ◽

Cited By ~ 14

Author(s):

Nicole Gerwin ◽

Gui-Quan Jia ◽

Robert Kulbacki ◽

José C. Gutierrez-Ramos

Keyword(s):

Growth Factors ◽

Preimplantation Embryo ◽

Preimplantation Development ◽

Preimplantation Embryos ◽

Positive Staining ◽

Polypeptide Growth Factors ◽

Mammalian Embryogenesis ◽

Genes Encoding ◽

Early Phases

Control of growth and differentiation during mammalian embryogenesis is regulated by growth factors from embryonic and/or maternal sources. Cytokines are polypeptide growth factors that are released by a variety of activated immune and nonimmune cells. To identify novel members of the cytokine family that could be involved in the growth and differentiation of the preimplantation embryo, we studied the expression pattern of several genes encoding cytokines and their receptors during mouse preimplantation developmentin vitroWe found that poly(A)+mRNAs for IL-1, IL-3, IL-6, IL-7, and TNFαare differentially expressed at several stages of mouse preimplantation development, including unfertilized oocytes. Immunostaining of preimplantation embryos using monoclonal antibodies specific for several cytokines and their receptors revealed that at least some of these mRNAs are translated into mature proteins during preimplantation development (IL-1, IL-6, and TNFα). Positive staining for IL-1 and IL-6 receptors was also detected at these stages of development. The controlled expression of these “inflammatory-type” cytokines and their receptors suggests a role for these growth factors during the early phases of mouse ontogeny.

Download Full-text