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

Research output: Contribution to journalJournal articleResearchpeer-review

  • Zarah M Löf-Öhlin
  • Pia Nyeng
  • Matthew E Bechard
  • Katja Hess
  • Eric Bankaitis
  • Thomas U Greiner
  • Jacqueline Ameri
  • Christopher V Wright
  • Semb, Tor Henrik

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.

Original languageEnglish
JournalNature Cell Biology
Issue number11
Pages (from-to)1313-1325
Number of pages13
Publication statusPublished - Nov 2017

    Research areas

  • Animals, Basic Helix-Loop-Helix Transcription Factors/metabolism, Cell Differentiation/physiology, Cell Polarity/physiology, Epithelial Cells/metabolism, Insulin-Secreting Cells/metabolism, Mice, Mice, Knockout, Morphogenesis/physiology, Nerve Tissue Proteins/metabolism, Neuropeptides/metabolism, Organogenesis/physiology, Phosphatidylinositol 3-Kinases/metabolism, Protein Kinase C/metabolism, Receptor, Epidermal Growth Factor/metabolism, Signal Transduction/physiology, rac1 GTP-Binding Protein/metabolism

ID: 193665556