期刊
DEVELOPMENT
卷 134, 期 23, 页码 4297-4306出版社
COMPANY BIOLOGISTS LTD
DOI: 10.1242/dev.009282
关键词
PAR1 (MARK); aPKC; ciliated cell; apical-basal polarity; Xenopus; epidermis; notch; ectoderm; XDelta-1 (DII1)
资金
- Biotechnology and Biological Sciences Research Council [BB/D010640/1] Funding Source: Medline
- Biotechnology and Biological Sciences Research Council [BB/D010640/1] Funding Source: researchfish
- BBSRC [BB/D010640/1] Funding Source: UKRI
Partitioning-defective 1 (PAR1) and atypical protein kinase C (aPKC) are conserved serine/threonine protein kinases implicated in the establishment of cell polarity in many species from yeast to humans. Here we investigate the roles of these protein kinases in cell fate determination in Xenopus epidermis. Early asymmetric cell divisions at blastula and gastrula stages give rise to the superficial (apical) and the deep (basal) cell layers of epidermal ectoderm. These two layers consist of cells with different intrinsic developmental potential, including superficial epidermal cells and deep ciliated cells. Our gain-and loss- of-function studies demonstrate that aPKC inhibits ciliated cell differentiation in Xenopus ectoderm and promotes superficial cell fates. We find that the crucial molecular substrate for aPKC is PAR1, which is localized in a complementary domain in superficial ectoderm cells. We show that PAR1 acts downstream of aPKC and is sufficient to stimulate ciliated cell differentiation and inhibit superficial epidermal cell fates. Our results suggest that aPKC and PAR1 function sequentially in a conserved molecular pathway that links apical-basal cell polarity to Notch signaling and cell fate determination. The observed patterning mechanism may operate in a wide range of epithelial tissues in many species.
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