p120ctn-Mediated Organ Patterning Precedes and Determines Pancreatic Progenitor Fate.

Nyeng P, Heilmann S, Löf-Öhlin ZM, Pettersson NF, Hermann FM, Reynolds AB, Semb H
Dev Cell. 2019 49 (1): 31-47.e9

PMID: 30853440 · DOI:10.1016/j.devcel.2019.02.005

The mechanism of how organ shape emerges and specifies cell fate is not understood. Pancreatic duct and endocrine lineages arise in a spatially distinct domain from the acinar lineage. Whether these lineages are pre-determined or settle once these niches have been established remains unknown. Here, we reconcile these two apparently opposing models, demonstrating that pancreatic progenitors re-localize to establish the niche that will determine their ultimate fate. We identify a p120ctn-regulated mechanism for coordination of organ architecture and cellular fate mediated by differential E-cadherin based cell sorting. Reduced p120ctn expression is necessary and sufficient to re-localize a subset of progenitors to the peripheral tip domain, where they acquire an acinar fate. The same mechanism is used re-iteratively during endocrine specification, where it balances the choice between the alpha and beta cell fates. In conclusion, organ patterning is regulated by p120ctn-mediated cellular positioning, which precedes and determines pancreatic progenitor fate.

Copyright © 2019 Elsevier Inc. All rights reserved.

MeSH Terms (18)

Animals Body Patterning Cadherins Catenins Cell Differentiation Cell Lineage Cell Movement Embryonic Development Flow Cytometry Gene Expression Regulation, Developmental Humans Islets of Langerhans Mice Pancreas Pancreatic Ducts Receptors, Notch Signal Transduction Stem Cells

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