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Löf-Öhlin, Z.M.* ; Nyeng, P.* ; Bechard, M.E.* ; Hess, K.* ; Bankaitis, E.* ; Greiner, T.U.* ; Ameri, J.* ; Wright, C.V.* ; Semb, H.*

EGFR signalling controls cellular fate and pancreatic organogenesis by regulating apicobasal polarity.

Nat. Cell Biol. 19, 1313-1325 (2017)
DOI PMC
Open Access Green as soon as Postprint is submitted to ZB.
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
ISSN (print) / ISBN 1465-7392
e-ISSN 1476-4679
Journal Nature Cell Biology
Quellenangaben Volume: 19, Issue: 11, Pages: 1313-1325 Article Number: , Supplement: ,
Publisher Nature Publishing Group
Reviewing status Peer reviewed
Institute(s) Institute of Transl. Stem Cell Research (ITS)