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p120ctn-Mediated Organ Patterning Precedes and Determines Pancreatic Progenitor Fate
Novo Nordisk Foundation Center for Stem Cell Biology (Danstem), University of Copenhagen, Copenhagen, Denmark.
Novo Nordisk Foundation Center for Stem Cell Biology (Danstem), University of Copenhagen, Copenhagen, Denmark.
Örebro University, School of Medical Sciences. Örebro University Hospital. Department for the Clinical Research Laboratory.
Department of Experimental Medical Sciences, Immunology, Lund University, Lund, Sweden.
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2019 (English)In: Developmental Cell, ISSN 1534-5807, E-ISSN 1878-1551, Vol. 49, no 1, p. 31-47Article in journal (Refereed) Published
Abstract [en]

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.

Place, publisher, year, edition, pages
CELL PRESS , 2019. Vol. 49, no 1, p. 31-47
National Category
Cell and Molecular Biology Developmental Biology
Identifiers
URN: urn:nbn:se:oru:diva-73869DOI: 10.1016/j.devcel.2019.02.005ISI: 000463822400006PubMedID: 30853440Scopus ID: 2-s2.0-85063387741OAI: oai:DiVA.org:oru-73869DiVA, id: diva2:1306356
Funder
Novo Nordisk, NNF17CC0027852
Note

Funding Agency:

JDRF  3-2011-214

Available from: 2019-04-23 Created: 2019-04-23 Last updated: 2019-04-23Bibliographically approved

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CiteExportLink to record
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Citation style
  • apa
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