We have updated our privacy policy. If you have any question, contact us at privacy@scicrunch.org. Dismiss and don't show again

Searching across hundreds of databases

Our searching services are busy right now. Your search will reload in five seconds.

Forgot Password

If you have forgotten your password you can enter your email here and get a temporary password sent to your email.

A dosage-dependent requirement for Sox9 in pancreatic endocrine cell formation.

Developmental biology | Nov 1, 2008

We have previously shown the transcription factor SOX9 to be required for the maintenance of multipotential pancreatic progenitor cells in the early embryonic pancreas. However, the association of pancreatic endocrine defects with the Sox9-haploinsufficiency syndrome campomelic dysplasia (CD) implies additional later roles for Sox9 in endocrine development. Using short-term lineage tracing in mice, we demonstrate here that SOX9 marks a pool of multipotential pancreatic progenitors throughout the window of major cell differentiation. During mid-pancreogenesis, both endocrine and exocrine cells simultaneously arise from the SOX9(+) epithelial cords. Our analysis of mice with 50%-reduced Sox9 gene dosage in pancreatic progenitors reveals endocrine-specific defects phenocopying CD. By birth, these mice display a specific reduction in endocrine cell mass, while their exocrine compartment and total organ size is normal. The decrease in endocrine cells is caused by reduced generation of endocrine progenitors from the SOX9(+) epithelium. Conversely, formation of exocrine progenitors is insensitive to reduced Sox9 gene dosage, thus explaining the normal organ size at birth. Our results show that not only is SOX9 required for the maintenance of early pancreatic progenitors, but also governs their adoption of an endocrine fate. Our findings therefore suggest that defective endocrine specification might underlie the pancreatic phenotype of individuals with CD.

Pubmed ID: 18723011 RIS Download

Mesh terms: Animals | Cell Differentiation | Cell Lineage | Embryo, Mammalian | Endocrine Glands | Epithelial Cells | Gene Dosage | Gene Expression Regulation, Developmental | Glucagon | Insulin | Islets of Langerhans | Mice | Mice, Transgenic | Morphogenesis | Pancreas | Pancreas, Exocrine | SOX9 Transcription Factor

Research resources used in this publication

None found

Research tools detected in this publication

None found

Data used in this publication

None found

Associated grants

  • Agency: NIDDK NIH HHS, Id: R01 DK068471
  • Agency: NIDDK NIH HHS, Id: R01 DK068471-03
  • Agency: NIDDK NIH HHS, Id: R01 DK078803
  • Agency: NIDDK NIH HHS, Id: R01 DK068471-04
  • Agency: NIDDK NIH HHS, Id: R01 DK078803-01
  • Agency: NIDDK NIH HHS, Id: R01 DK68471-01
  • Agency: NIDDK NIH HHS, Id: R01 DK078803-02

Mouse Genome Informatics (Data, Gene Annotation)

Publication data is provided by the National Library of Medicine ® and PubMed ®. Data is retrieved from PubMed ® on a weekly schedule. For terms and conditions see the National Library of Medicine Terms and Conditions.

We have not found any resources mentioned in this publication.