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

Research output: Contribution to journalArticle

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 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.

Details

Authors
  • Zarah M. Löf-Öhlin
  • Pia Nyeng
  • Matthew E. Bechard
  • Katja Hess
  • Eric Bankaitis
  • Thomas U. Greiner
  • Jacqueline Ameri
  • Christopher V. Wright
  • Henrik Semb
Organisations
External organisations
  • University of Copenhagen
  • Vanderbilt University
Research areas and keywords

Subject classification (UKÄ) – MANDATORY

  • Cell Biology
Original languageEnglish
Pages (from-to)1313-1325
Number of pages13
JournalNature Cell Biology
Volume19
Issue number11
Publication statusPublished - 2017 Nov 1
Publication categoryResearch
Peer-reviewedYes