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

Löf-Öhlin, Zarah M. LU ; Nyeng, Pia LU ; Bechard, Matthew E.; Hess, Katja LU ; Bankaitis, Eric; Greiner, Thomas U. LU ; Ameri, Jacqueline LU ; Wright, Christopher V. and Semb, Henrik LU (2017) In Nature Cell Biology 19(11). p.1313-1325
Abstract

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... (More)

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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author
organization
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type
Contribution to journal
publication status
published
subject
in
Nature Cell Biology
volume
19
issue
11
pages
13 pages
publisher
Nature Publishing Group
external identifiers
  • scopus:85032618059
  • wos:000415069100006
ISSN
1465-7392
DOI
10.1038/ncb3628
language
English
LU publication?
yes
id
537a0ccb-c56f-47fb-b449-f8f05021e744
date added to LUP
2017-11-10 10:25:39
date last changed
2018-02-10 03:00:03
@article{537a0ccb-c56f-47fb-b449-f8f05021e744,
  abstract     = {<p>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.</p>},
  author       = {Löf-Öhlin, Zarah M. and Nyeng, Pia and Bechard, Matthew E. and Hess, Katja and Bankaitis, Eric and Greiner, Thomas U. and Ameri, Jacqueline and Wright, Christopher V. and Semb, Henrik},
  issn         = {1465-7392},
  language     = {eng},
  month        = {11},
  number       = {11},
  pages        = {1313--1325},
  publisher    = {Nature Publishing Group},
  series       = {Nature Cell Biology},
  title        = {EGFR signalling controls cellular fate and pancreatic organogenesis by regulating apicobasal polarity},
  url          = {http://dx.doi.org/10.1038/ncb3628},
  volume       = {19},
  year         = {2017},
}