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Nyeng, P.* ; Heilmann, S.* ; Löf-Öhlin, Z.M.* ; Pettersson, N.F.* ; Hermann, F.M.* ; Reynolds, A.B.* ; Semb, H.

P120ctn-mediated organ patterning precedes and determines pancreatic progenitor fate.

Dev. Cell 49, 31-47.e9 (2019)
Publ. Version/Full Text Research data DOI PMC
Open Access Green as soon as Postprint is submitted to ZB.
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.
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Publication type Article: Journal article
Document type Scientific Article
Keywords Beta Cell ; Cell Segregation ; Ctnnd1 ; Development ; Differentiation ; Niche ; P120ctn ; Pancreas ; Patterning ; Progenitor; P120 Catenin; E-cadherin; Intercellular-adhesion; Acinar Development; Cell; Organogenesis; Dynamics; Lineage; Tubulogenesis; Expression
Language english
Publication Year 2019
HGF-reported in Year 2019
ISSN (print) / ISBN 1534-5807
e-ISSN 1878-1551
Journal Developmental Cell
Quellenangaben Volume: 49, Issue: 1, Pages: 31-47.e9 Article Number: , Supplement: ,
Publisher Elsevier
Publishing Place 50 Hampshire St, Floor 5, Cambridge, Ma 02139 Usa
Reviewing status Peer reviewed
Institute(s) Institute of Transl. Stem Cell Research (ITS)
POF-Topic(s) 30201 - Metabolic Health
Research field(s) Helmholtz Diabetes Center
PSP Element(s) G-506800-001
DOI 10.1016/j.devcel.2019.02.005
WOS ID WOS:000463822400006
Scopus ID 85063387741
PubMed ID 30853440
Erfassungsdatum 2019-03-29
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