ROCK-nmMyoII, Notch and gene-dosage link epithelial morphogenesis with cell fate in the pancreatic endocrine-progenitor niche.

Bankaitis ED, Bechard ME, Gu G, Magnuson MA, Wright CVE
Development. 2018 145 (18)

PMID: 30126902 · PMCID: PMC6176929 · DOI:10.1242/dev.162115

During mouse pancreas organogenesis, endocrine cells are born from progenitors residing in an epithelial plexus niche. After a period in a lineage-primed state, progenitors become endocrine committed via upregulation of We find that the to transition is associated with distinct stages of an epithelial egression process: narrowing the apical surface of the cell, basalward cell movement and eventual cell-rear detachment from the apical lumen surface to allow clustering as nascent islets under the basement membrane. Apical narrowing, basalward movement and transcriptional upregulation still occur without Neurog3 protein, suggesting that morphogenetic cues deployed within the plexus initiate endocrine commitment upstream or independently of Neurog3. Neurog3 is required for cell-rear detachment and complete endocrine-cell birth. The ROCK-nmMyoII pathway coordinates epithelial-cell morphogenesis and the progression through -expressing states. NmMyoII is necessary for apical narrowing, basalward cell displacement and upregulation, but all three are limited by ROCK activity. We propose that ROCK-nmMyoII activity, gene-dose and Notch signaling integrate endocrine fate allocation with epithelial plexus growth and morphogenesis, representing a feedback control circuit that coordinates morphogenesis with lineage diversification in the endocrine-birth niche.

© 2018. Published by The Company of Biologists Ltd.

MeSH Terms (15)

Animals Basic Helix-Loop-Helix Transcription Factors Cell Differentiation Cell Movement Endocrine Cells Gene Dosage Mice Mice, Transgenic Nerve Tissue Proteins Organogenesis Pancreas Receptors, Notch rho-Associated Kinases Stem Cells Transcriptional Activation

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