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

Zarah Löf-Öhlin, Pia Nyeng, M. E. Bechard, Katja Hess, E Bankaitis, TU Greiner, J. Ameri, CV Wright, Henrik Semb

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

Resumé

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.
OriginalsprogEngelsk
TidsskriftNature Cell Biology
Sider (fra-til)1313–1325
ISSN1465-7392
DOI
StatusUdgivet - 1 nov. 2017
Udgivet eksterntJa

Citer dette

Löf-Öhlin, Z., Nyeng, P., Bechard, M. E., Hess, K., Bankaitis, E., Greiner, TU., ... Semb, H. (2017). EGFR signalling controls cellular fate and pancreatic organogenesis by regulating apicobasal polarity. Nature Cell Biology, 1313–1325. https://doi.org/10.1038/ncb3628
Löf-Öhlin, Zarah ; Nyeng, Pia ; Bechard, M. E. ; Hess, Katja ; Bankaitis, E ; Greiner, TU ; Ameri, J. ; Wright, CV ; Semb, Henrik. / EGFR signalling controls cellular fate and pancreatic organogenesis by regulating apicobasal polarity. I: Nature Cell Biology. 2017 ; s. 1313–1325.
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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.",
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Löf-Öhlin, Z, Nyeng, P, Bechard, ME, Hess, K, Bankaitis, E, Greiner, TU, Ameri, J, Wright, CV & Semb, H 2017, 'EGFR signalling controls cellular fate and pancreatic organogenesis by regulating apicobasal polarity', Nature Cell Biology, s. 1313–1325. https://doi.org/10.1038/ncb3628

EGFR signalling controls cellular fate and pancreatic organogenesis by regulating apicobasal polarity. / Löf-Öhlin, Zarah; Nyeng, Pia; Bechard, M. E.; Hess, Katja; Bankaitis, E; Greiner, TU; Ameri, J.; Wright, CV; Semb, Henrik.

I: Nature Cell Biology, 01.11.2017, s. 1313–1325.

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

TY - JOUR

T1 - EGFR signalling controls cellular fate and pancreatic organogenesis by regulating apicobasal polarity

AU - Löf-Öhlin, Zarah

AU - Nyeng, Pia

AU - Bechard, M. E.

AU - Hess, Katja

AU - Bankaitis, E

AU - Greiner, TU

AU - Ameri, J.

AU - Wright, CV

AU - Semb, Henrik

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N2 - 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.

AB - 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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