EGFR signalling controls cellular fate and pancreatic organogenesis by regulating apicobasal polarity
| Autor: | Katja Hess, Jacqueline Ameri, Henrik Semb, Eric D. Bankaitis, Matthew E. Bechard, Pia Nyeng, Thomas U. Greiner, Zarah M. Löf-Öhlin, Christopher V.E. Wright |
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| Rok vydání: | 2017 |
| Předmět: |
rac1 GTP-Binding Protein
0301 basic medicine Polarity (physics) Organogenesis Cellular differentiation Morphogenesis Notch signaling pathway Nerve Tissue Proteins RAC1 Biology Mice Phosphatidylinositol 3-Kinases 03 medical and health sciences Insulin-Secreting Cells Basic Helix-Loop-Helix Transcription Factors Animals Progenitor cell Protein Kinase C Mice Knockout Betacellulin Neuropeptides Cell Polarity Cell Differentiation Epithelial Cells Cell Biology Cell biology ErbB Receptors 030104 developmental biology Signal Transduction |
| Zdroj: | Nature Cell Biology. 19:1313-1325 |
| ISSN: | 1476-4679 1465-7392 |
| DOI: | 10.1038/ncb3628 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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