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p120ctn-Mediated Organ Patterning Precedes and Determines Pancreatic Progenitor Fate

Nyeng, Pia LU ; Heilmann, Silja ; Löf-Öhlin, Zarah M. LU ; Pettersson, Nina Fransén LU ; Hermann, Florian Malte ; Reynolds, Albert B. and Semb, Henrik LU (2019) In Developmental Cell 49(1). p.9-47
Abstract

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... (More)

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. Nyeng et al. use live imaging to demonstrate that differential p120-catenin expression segregates pancreatic progenitor cells into fate-determining niches by differential surface tension. While cells with low expression move to the periphery to become acinar cells, cells with high expression remain in the center to become duct and endocrine cells.

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author
; ; ; ; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
beta cell, cell segregation, CTNND1, development, differentiation, niche, p120ctn, pancreas, patterning, progenitor
in
Developmental Cell
volume
49
issue
1
pages
9 - 47
publisher
Cell Press
external identifiers
  • pmid:30853440
  • scopus:85063387741
ISSN
1534-5807
DOI
10.1016/j.devcel.2019.02.005
language
English
LU publication?
yes
id
ab4dd08e-15a9-4ab9-9c60-74d058128193
date added to LUP
2019-04-05 13:29:29
date last changed
2021-03-03 05:38:21
@article{ab4dd08e-15a9-4ab9-9c60-74d058128193,
  abstract     = {<p>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. Nyeng et al. use live imaging to demonstrate that differential p120-catenin expression segregates pancreatic progenitor cells into fate-determining niches by differential surface tension. While cells with low expression move to the periphery to become acinar cells, cells with high expression remain in the center to become duct and endocrine cells.</p>},
  author       = {Nyeng, Pia and Heilmann, Silja and Löf-Öhlin, Zarah M. and Pettersson, Nina Fransén and Hermann, Florian Malte and Reynolds, Albert B. and Semb, Henrik},
  issn         = {1534-5807},
  language     = {eng},
  number       = {1},
  pages        = {9--47},
  publisher    = {Cell Press},
  series       = {Developmental Cell},
  title        = {p120ctn-Mediated Organ Patterning Precedes and Determines Pancreatic Progenitor Fate},
  url          = {http://dx.doi.org/10.1016/j.devcel.2019.02.005},
  doi          = {10.1016/j.devcel.2019.02.005},
  volume       = {49},
  year         = {2019},
}