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EGFR signalling controls cellular fate and pancreatic organogenesis by regulating apicobasal polarity.
Nat. Cell Biol. 19, 1313-1325 (2017)
Apicobasal polarity is known to affect epithelial morphogenesis and cell differentiation, but it remains unknown how these processes are mechanistically orchestrated. We find that ligand-specific EGFR signalling via PI(3)K and Rac1 autonomously modulates apicobasal polarity to enforce the sequential control of morphogenesis and cell differentiation. Initially, EGF controls pancreatic tubulogenesis by negatively regulating apical polarity induction. Subsequently, betacellulin, working via inhibition of atypical protein kinase C (aPKC), causes apical domain constriction within neurogenin3+ endocrine progenitors, which results in reduced Notch signalling, increased neurogenin3 expression, and β-cell differentiation. Notably, the ligand-specific EGFR output is not driven at the ligand level, but seems to have evolved in response to stage-specific epithelial influences. The EGFR-mediated control of β-cell differentiation via apical polarity is also conserved in human neurogenin3+ cells. We provide insight into how ligand-specific EGFR signalling coordinates epithelial morphogenesis and cell differentiation via apical polarity dynamics.
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Publication type
Article: Journal article
Document type
Scientific Article
Language
english
Publication Year
2017
HGF-reported in Year
2017
ISSN (print) / ISBN
1465-7392
e-ISSN
1476-4679
Journal
Nature Cell Biology
Quellenangaben
Volume: 19,
Issue: 11,
Pages: 1313-1325
Publisher
Nature Publishing Group
Reviewing status
Peer reviewed
Institute(s)
Institute of Transl. Stem Cell Research (ITS)
DOI
10.1038/ncb3628
PubMed ID
29058721
Erfassungsdatum
2020-02-18