Bmp2 Signaling Regulates the Hepatic versus Pancreatic Fate Decision

Department of Biochemistry and Biophysics, Programs in Developmental Biology, Genetics and Human Genetics, University of California, San Francisco, 1550 4th Street, San Francisco, CA 94158, USA.
Developmental Cell (Impact Factor: 9.71). 12/2008; 15(5):738-48. DOI: 10.1016/j.devcel.2008.08.019
Source: PubMed


Explant culture data have suggested that the liver and pancreas originate from common progenitors. We used single-cell-lineage tracing in zebrafish to investigate this question in vivo as well as to analyze the hepatic versus pancreatic fate decision. At early somite stages, endodermal cells located at least two cells away from the midline can give rise to both liver and pancreas. In contrast, endodermal cells closer to the midline give rise to pancreas and intestine, but not liver. Loss- and gain-of-function analyses show that Bmp2b, expressed in the lateral plate mesoderm, signals through Alk8 to induce endodermal cells to become liver. When Bmp2b was overexpressed, medially located endodermal cells, fated to become pancreas and intestine, contributed to the liver. These data provide in vivo evidence for the existence of bipotential hepatopancreatic progenitors and indicate that their fate is regulated by the medio-lateral patterning of the endodermal sheet, a process controlled by Bmp2b.

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Available from: Won-Suk Chung
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    • "Although these studies map bipotential progenitors and the timing of their segregation into a liver or pancreas anlagen, it is thought that the fates of these segregated populations might be reversible in early somite stages such that modulation of extrinsic signals can shift one fate into another (Miki et al., 2012). In zebrafish, endodermal cells capable of both a liver and exocrine pancreas fate have been identified at the six-to eight-somite stage (Chung et al., 2008). Although these labeling studies localize bipotential progenitors, how this population spatially relates to multiple signals that regulate liver versus pancreas specification is poorly understood. "
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