期刊
DEVELOPMENT
卷 140, 期 21, 页码 4311-4322出版社
COMPANY BIOLOGISTS LTD
DOI: 10.1242/dev.093922
关键词
Lineage specification; Primitive endoderm; Epiblast; Mouse blastocyst; ICM; aPKC; GATA4; Pluripotency
资金
- Obra Social la Caixa
- University of Manchester
- Wellcome Trust Senior Research Fellowship [090868/Z/09]
- Manchester Fellowship
- Biotechnology and Biological Sciences Research Council (BBSRC) [BP R107861]
- Biotechnology and Biological Sciences Research Council [BB/G012393/1] Funding Source: researchfish
- BBSRC [BB/G012393/1] Funding Source: UKRI
During mouse pre-implantation development, extra-embryonic primitive endoderm (PrE) and pluripotent epiblast precursors are specified in the inner cell mass (ICM) of the early blastocyst in a 'salt and pepper' manner, and are subsequently sorted into two distinct layers. Positional cues provided by the blastocyst cavity are thought to be instrumental for cell sorting; however, the sequence of events and the mechanisms that control this segregation remain unknown. Here, we show that atypical protein kinase C (aPKC), a protein associated with apicobasal polarity, is specifically enriched in PrE precursors in the ICM prior to cell sorting and prior to overt signs of cell polarisation. aPKC adopts a polarised localisation in PrE cells only after they reach the blastocyst cavity and form a mature epithelium, in a process that is dependent on FGF signalling. To assess the role of aPKC in PrE formation, we interfered with its activity using either chemical inhibition or RNAi knockdown. We show that inhibition of aPKC from the mid blastocyst stage not only prevents sorting of PrE precursors into a polarised monolayer but concomitantly affects the maturation of PrE precursors. Our results suggest that the processes of PrE and epiblast segregation, and cell fate progression are interdependent, and place aPKC as a central player in the segregation of epiblast and PrE progenitors in the mouse blastocyst.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据