Developmental Cell
Volume 49, Issue 1, 8 April 2019, Pages 31-47.e9
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Article
p120ctn-Mediated Organ Patterning Precedes and Determines Pancreatic Progenitor Fate

https://doi.org/10.1016/j.devcel.2019.02.005Get rights and content
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Highlights

  • p120ctn expression segregates pancreatic progenitors into fate determining niches

  • p120ctn-low progenitors segregate into peripheral domains and form pro-acinar tips

  • p120ctn-high progenitors remain in the trunk to become duct and endocrine cells

  • p120ctn downregulation in endocrine cells drives delamination

Summary

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.

Keywords

niche
progenitor
p120ctn
CTNND1
cell segregation
development
pancreas
patterning
differentiation
beta cell

Cited by (0)

5

Present address: Department for the Clinical Research Laboratory, Örebro University Hospital, Örebro 70362, Sweden

6

Present address: Faculty of Medicine and Health, School of Medical Sciences, Örebro University, Örebro 70182, Sweden

7

Present address: Department of Experimental Medical Sciences, Immunology, Lund University, Lund, 22100, Sweden

8

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