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Nkx6 Transcription Factors and Ptf1a Function as Antagonistic Lineage Determinants in Multipotent Pancreatic Progenitors

Open access
Schaffer, Ashleigh E., Freude, Kristine K., Nelson, Shelley B., Sander, Maike·2010·Developmental Cell

Abstract

Summary The molecular mechanisms that underlie cell lineage diversification of multipotent progenitors in the pancreas are virtually unknown. Here, we show that the early fate choice of pancreatic progenitors between the endocrine and acinar cell lineage is restricted by cross-repressive interactions between the transcription factors Nkx6.1/Nkx6.2 (Nkx6) and Ptf1a. Using genetic loss- and gain-of-function approaches, we demonstrate that Nkx6 factors and Ptf1a are required and sufficient to repress the alternative lineage program and to specify progenitors toward an endocrine or acinar fate, respectively. The Nkx6/Ptf1a switch only operates during a critical competence window when progenitors are still multipotent and can be uncoupled from cell differentiation. Thus, cross-antagonism between Nkx6 and Ptf1a in multipotent progenitors governs the equilibrium between endocrine and acinar cell neogenesis required for normal pancreas development.

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Crossref · 10.1016/j.devcel.2010.05.015

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Authors
Schaffer, A. E., Freude, K. K., Nelson, S. B., & Sander, M.
Venue
Developmental Cell
Publisher
Elsevier BV
Published
2010-06
Volume
18
Issue
6
Pages
1022-1029
ISSN
1534-5807 (ISSN-L)
OpenAlex
W2110982118
Cited by
279
References
0
FWCI
17.39
Type
journal article
Language
en
Open access
bronze

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