Ability of outside cells from preimplantation mouse embryos to form inner cell mass derivatives

Rossant, Janet; Vijh, K. M.

doi:10.1016/0012-1606(80)90395-4

Cited by 105 publications

(51 citation statements)

References 6 publications

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“…Definite pattern formation in relation to embryo morphology is achieved in a second phase in which a sorting mechanism establishes a relationship between the molecular signature of a blastomere and its position within the conceptus. This model is consistent with the highly regulative capacity of the early mouse embryo until late blastocyst stage (Rossant and Lis, 1979;Rossant and Vijh, 1980): the fate of blastomeres is not determined irreversibly until blastocyst morphogenesis is completed. Thus, we conclude that the first lineages may emerge after the 8-cell stage, possibly due to stochastic processes and/or asymmetric cell divisions.…”

Section: Autonomous Emergence Of Asymmetries In the Early Mouse Embryosupporting

confidence: 84%

Stochastic patterning in the mouse pre-implantation embryo

2007

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Mouse pre-implantation development gives rise to the blastocyst, which is made up of at least three distinct cell types: the trophectoderm (TE) that surrounds a cavity, and an inner cell mass (ICM) comprising the primitive endoderm (PE) and epiblast (EPI). However, the underlying mechanisms involved in patterning the cleavage-stage embryo are still unresolved. By analyzing the distribution of the transcription factors Oct4 (Pou5f1), Cdx2 and Nanog at precisely defined stages in pre-implantation development, we were able to identify critical events leading to the divergence of TE, EPI and PE lineages. We found that Oct4 is present in all cells until late blastocyst, gradually disappearing from the TE thereafter. The expression patterns of both Cdx2 and Nanog exhibit two specific phases, culminating in their restriction to TE and EPI, respectively. In the first phase, starting after compaction, blastomeres show highly variable Cdx2 and Nanog protein levels. Importantly, the variability in Nanog levels is independent of position within the morula, whereas Cdx2 variability may originate from asymmetric cell divisions at the 8-cell stage in a non-stereotypic way. Furthermore, there is initially no reciprocal relationship between Cdx2 and Oct4 or between Cdx2 and Nanog protein levels. In the second phase, a definite pattern is established, possibly by a sorting process that accommodates intrinsic and extrinsic cues. Based on these results, we propose a model in which early embryonic mouse patterning includes stochastic processes, consistent with the highly regulative capacity of the embryo. This may represent a feature unique to early mammalian development.

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Section: Autonomous Emergence Of Asymmetries In the Early Mouse Embryosupporting

confidence: 84%

Stochastic patterning in the mouse pre-implantation embryo

2007

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“…The committed pluripotent cells in which Nanog has an essential function in maintaining, cells such as the ESC and those found in the epiblast of the expanded blastocyst, are developmentally distinct from their totipotent precursors. Although Nanog transcripts first appear in the inner cells of the morula, cells in the preimplantation mouse conceptus do not become committed to either the trophoblast or the epiblast lineage until after blastocyst formation (27,28). This epiblast commitment, something that does not occur in Oct4 null blastocysts (5), may be associated with the onset of Oct4 regulation of Nanog.…”

Section: Discussionmentioning

confidence: 99%

Transcriptional Regulation of Nanog by OCT4 and SOX2

Rodda¹,

Chew

Lim

et al. 2005

Journal of Biological Chemistry

1,015

870

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Nanog, Sox2, and Oct4 are transcription factors all essential to maintaining the pluripotent embryonic stem cell phenotype. Through a cooperative interaction, Sox2 and Oct4 have previously been described to drive pluripotent-specific expression of a number of genes. We now extend the list of Sox2-Oct4 target genes to include Nanog. Within the Nanog proximal promoter, we identify a composite sox-oct cis-regulatory element essential for Nanog pluripotent transcription. This element is conserved over 250 million years of cumulative evolution within the eutherian mammals. A Nanog proximal promoter-EGFP (enhanced green fluorescent protein) reporter transgene recapitulates endogenous Nanog mRNA expression in embryonic stem cells and their differentiated derivatives. Sox2 and Oct4 interaction with the Nanog promoter was confirmed through mutagenesis and in vitro binding assays. Electrophoretic mobility shift assays indicate that the Sox2-Oct4 heterodimer forms more efficiently on the composite element within Nanog than the similar element within Fgf4. Using chromatin immunoprecipitation, we show that Oct4 and Sox2 bind to the Nanog promoter in living mouse and human embryonic stem cells. Furthermore, by specific knockdown of Oct4 and Sox2 mRNA by RNA interference in embryonic stem cells, we provide genetic evidence for a link between Oct4, Sox2, and the Nanog promoter. These studies extend the understanding of the pluripotent genetic regulatory network within which the Sox2-Oct4 complex are at the top of the regulatory hierarchy.Nanog is a homeobox-containing transcription factor with an essential function in maintaining the pluripotent cells of the inner cell mass and in the derivation of embryonic stem cells (ESCs) 1 from these (1). Furthermore, overexpression of Nanog is capable of maintaining the pluripotency and self-renewing characteristics of ESCs under what normally would be differentiation-inducing culture conditions (2). Concomitant with this essential function in pluripotent cell maintenance is its restricted expression pattern. Nanog transcripts first appear in the inner cells of the morula prior to blastocyst formation (1, 2), are restricted to the inner cell mass in the blastocyst (3), and are no longer detectable at implantation. Expression of Nanog reappears in the proximal epiblast at embryonic day 6 and remains restricted to the epiblast as development progresses (4). The factors controlling expression of this gene have yet to be described. The POU domain-containing Oct4 and the HMG domaincontaining Sox2 are two other transcription factors known to be essential for normal pluripotent cell development and maintenance (5, 6). Although both have independent roles in determining other cell types (6, 7), at least part of their function in pluripotent cells is via a synergistic interaction between the two to drive transcription of target genes. Currently known targets of Sox2-Oct4 synergy are Fgf4, Utf1, and Fbx15, as well as Sox2 and Pou5f1 (the gene encoding Oct4) themselves (8 -13). Each of these targe...

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“…The outer cells of the blastocyst, which are polarized, give rise to the trophectoderm, whereas cells in the interior, which are not polarized, give rise to the inner cell mass (Figure 1) (6). Interestingly, these initial events do not irreversibly establish the extraembryonic and embryonic murine lineages: the polarized outer cells can contribute to the inner cell mass (7), and the inner cells retain the ability to differentiate into trophectoderm (S2). Whether human blastomeres exhibit a similar degree of plasticity is unknown.…”

Section: Implantationmentioning

confidence: 99%