How to lose your inheritance

Laird, Diana J.

doi:10.1038/d41586-018-06849-5

Cited by 2 publications

(2 citation statements)

References 13 publications

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“…Whereas overexpression of Otx2 decreases the number of PGCs, the absence of Otx2 augments the number of PGCs, indicating a negative correlation between PGCs and Otx2 expression (Zhang et al, 2018). Although these experiments lacked the sensitivity to detect low levels of Otx2, the question remains whether PGC precursors that incompletely extinguish Otx2 become PGCs with low levels of somatic gene expression that parlay into measurable differences in behavior (Laird, 2018).…”

Section: Pgc Specification By Induction-mentioning

confidence: 99%

Heterogeneity of primordial germ cells

Nguyen

Jaszczak

Laird

2019

Current Topics in Developmental Biology

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Primordial germ cells (PGCs) must complete a complex and dynamic developmental program during embryogenesis to establish the germline. This process is highly conserved and involves a diverse array of tasks required of PGCs, including migration, survival, sex differentiation, and extensive epigenetic reprogramming. A common theme across many organisms is that PGC success is heterogeneous: only a portion of all PGCs complete all these steps while many other PGCs are eliminated from further germline contribution. The differences that distinguish successful PGCs as a population are not well understood. Here, we examine variation that exists in PGCs as they navigate the many stages of this developmental journey. We explore potential sources of PGC heterogeneity and their potential implications in affecting germ cell behaviors. Lastly, we discuss the potential for PGC development to function as a multistage selection process that assesses heterogeneity in PGCs to refine germline quality.

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Section: Pgc Specification By Induction-mentioning

confidence: 99%

Heterogeneity of primordial germ cells

Nguyen

Jaszczak

Laird

2019

Current Topics in Developmental Biology

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“…Moreover, in pluripotent cells OTX2 may also bind to the enhancer region of Oct4, Nanog and Sox2 (Acampora et al, 2016). Recent work has revealed that OTX2 is a novel crucial determinant controlling germline entry of formative epiblast cells in mouse (Zhang et al, 2018;Zhang and Chambers, 2019;Laird, 2018). Indeed, by restricting germline entry to a limited number of epiblast-derived cells, OTX2 controls segregation of germ cells from somatic precursors.…”

Section: Introductionmentioning

confidence: 99%

Direct repression of Nanog and Oct4 by OTX2 modulates the contribution of epiblast-derived cells to germline and somatic lineage

et al. 2021

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In mammals, the pre-gastrula proximal epiblast gives rise to primordial germ cells (PGCs) or somatic precursors in response to BMP4 and WNT signaling. Entry into the germline requires activation of a naïve-like pluripotency gene regulatory network (GRN). Recent work has shown that suppression of OTX2 expression in the epiblast by BMP4 allows cells to develop a PGC fate in a precise temporal window. However, the mechanisms by which OTX2 suppresses PGC fate are unknown. Here, we show that, in mice, OTX2 prevents epiblast cells from activating the pluripotency GRN by direct repression of Oct4 and Nanog. Loss of this control during PGC differentiation in vitro causes widespread activation of the pluripotency GRN and a deregulated response to LIF, BMP4 and WNT signaling. These abnormalities, in specific cell culture conditions, result in massive germline entry at the expense of somatic mesoderm differentiation. Increased generation of PGCs also occurs in mutant embryos. We propose that the OTX2-mediated repressive control of Oct4 and Nanog is the basis of the mechanism that determines epiblast contribution to germline and somatic lineage.

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How to lose your inheritance

Cited by 2 publications

References 13 publications

Heterogeneity of primordial germ cells

Heterogeneity of primordial germ cells

Direct repression of Nanog and Oct4 by OTX2 modulates the contribution of epiblast-derived cells to germline and somatic lineage

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