Cell division and cell allocation in early mouse development

Abstract

Cell division was observed in intact and dissociated mouse embryos between the 2-cell stage and the blastocyst in embryos developing in culture. Division to the 4-cell stage was usually asynchronous. The first cell to divide to the 4-cell stage produced descendants which tended to divide ahead of those cells produced by its slow partner at all subsequent stages of development up to the blastocyte stage. The descendants of the first cell to divide to the 4-cell stage did not subsequently have short cell cycles. The first cell or last cell to divide from the 4-cell stage was labelled with tritiated thymidine. The embryo was reassembled, and it was found that the first pair of cells to reach the 8-cell stage contributed disproportionately more descendants to the ICM when compared with the last cell to divide to the 8-cell stage.

Temporal variability and cell mechanics control robustness in mammalian embryogenesis

“…Although cell-lineage has been established for many species, few studies focused on the cell-to-cell variability in spatial arrangement or cleavage timing (Anderson et al, 2017; Kelly et al, 1978; Olivier et al, 2010; Van et al, 1981; Villoutreix et al, 2016), with the exception of active desynchronisation described in Ascidian embryos (Dumollard et al, 2013; Dumollard et al, 2017; Sallé and Minc, 2022) and in human embryos (Mashiko et al, 2022; Roux, 1995). With a small number of cells and progressively accumulating variabilities in space and time, early mammalian embryos present an excellent opportunity to measure the building of variabilities during development.…”

“…Not only gene expression, but other mechanical and temporal parameters exhibit measurable variability within and between embryos that may affect patterning and morphogenesis. For instance, the 2 nd cleavage orientation was shown to be random (Louvet-Vallée et al, 2005); the variability in cleavage timing has been suggested to impact cell-fate segregation (Kelly et al, 1978; Mashiko et al, 2022); the nuclear-cytoplasmic ratio has been linked to cell differentiation (Aiken et al, 2004); and heterogeneity in cell contractility was shown to drive cell sorting in 16-cell stage mouse embryo (Maître et al, 2016; Samarage et al, 2015) while cell-to-cell variability in cellular fluidity may contribute to the segregation of primitive endoderm and epiblast in blastocysts (Yanagida et al, 2022). Although recent studies in mouse showed that at least some of these variabilities are regulated by the feedbacks between cell polarity, tissue mechanics and gene expression (Maître et al, 2016; Korotkevich et al, 2017), the role that intercellular variabilities may play in development and its robustness has not been explored yet.…”

Analysis of mice (Mus Musculus L.) and hamster embryo development using culture and vitrification medium: Systematic review

“…Embryo aggregation or embryo fusion to produce embryos with high viability values can be carried out at an early stage of embryonic development until before the embryo reaches the compact morula stage ( Kelly et al , 1978 ). In this study, the embryos used in the aggregation process were embryos with an 8-cell division stage and were proven to be capable of producing embryos with high viability values.…”

Patterning of the embryo: the first spatial decisions in the life of a mouse

“…But previous conclusions seemed somewhat conflicting. Whereas some studies showed that the earlier dividing blastomeres made a disproportionate contribution to the ICM (Kelly et al, 1978;Graham and Deussen, 1978;Spindle, 1982;Surani and Barton, 1984;Garbutt et al, 1987a), another showed that they had a tendency to be associated with the nascent blastocoel and thus the abembryonic region of the blastocyst (Garbutt et al, 1987b). As a result, the significance of the order of division for embryonic polarity remained unsettled.…”

“…Tarkowski and Wroblewska found that such capacity became limited during cleavage and that isolated, individual four-or eight-cell mouse blastomeres formed mainly trophectoderm rather than a normal blastocyst (Tarkowski and Wroblewska, 1967). This limitation did not however arise from lack of differentiative capacity, because all four-cell mouse blastomeres and at least some eight-cell, 16cell and even ICM cells maintain the ability to contribute to both ICM and trophectoderm lineages when combined with cells from other embryos to produce chimeras (Rossant, 1975;Rossant, 1976;Kelly, 1977;Kelly et al, 1978;Rossant and Lis, 1979;Rossant and Vijh, 1980;Tarkowski et al, 2001). Such studies revealing the plasticity of mammalian embryos led to the development of the key concept that the position of a blastomere within the embryo is important for its future destiny.…”