title: SOX4 cooperates with neurogenin 3 to regulate endocrine pancreas formation in mouse models.
abstract: OBJECTIVE
  The sex-determining region Y (SRY)-related high mobility group (HMG) box (SOX) family of transcription factors is essential for normal organismal development. Despite the longstanding knowledge that many SOX family members are expressed during pancreas development, a role for many of these factors in the establishment of insulin-producing beta cell fate remains to be determined. The aim of this study is to elucidate the role of SOX4 during beta cell development.
  
  
  METHODS
  We used pancreas and endocrine progenitor mouse knockouts of Sox4 to uncover the roles of SOX4 during pancreas development. Lineage tracing and in vitro models were used to determine how SOX4 regulates beta cell formation and understand the fate of Sox4-null endocrine lineage cells.
  
  
  RESULTS
  This study demonstrates a progenitor cell-autonomous role for SOX4 in regulating the genesis of beta cells and shows that it is required at multiple stages of the process. SOX4 deletion in the multipotent pancreatic progenitors resulted in impaired endocrine progenitor cell differentiation. Deletion of SOX4 later in the Neurog3-expressing cells also caused reductions in beta cells. Lineage studies showed loss of Sox4 in endocrine progenitors resulted in a block in terminal islet cell differentiation that was attributed to reduction in the production of key beta cell specification factors.
  
  
  CONCLUSIONS
  These results demonstrate that SOX4 is essential for normal endocrine pancreas development both concomitant with, and downstream of, the endocrine fate decision. In conclusion, these studies position Sox4 temporally in the endocrine differentiation programme and provide a new target for improving in vitro differentiation of glucose-responsive pancreatic beta cells.
authors: Diabetes Research Program, Child and Family Research Institute, A4-184, 950 West 28 Ave, Vancouver, BC, V5Z 4H4, Canada.
authors: Eric E
authors: EE
authors: Xu
authors: Nicole A J
authors: NA
authors: Krentz
authors: Sara
authors: S
authors: Tan
authors: Sam Z
authors: SZ
authors: Chow
authors: Mei
authors: M
authors: Tang
authors: Cuilan
authors: C
authors: Nian
authors: Francis C
authors: FC
authors: Lynn
mesh_terms: D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics / Q000378:metabolism*; D002454:Cell Differentiation / Q000235:genetics; D018507:Gene Expression Regulation, Developmental; D050417:Insulin-Secreting Cells / Q000378:metabolism; D007515:Islets of Langerhans / Q000196:embryology* / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D038081:Organogenesis / Q000235:genetics*; D055751:SOXC Transcription Factors / Q000235:genetics / Q000378:metabolism*
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D009419:Nerve Tissue Proteins; D055751:SOXC Transcription Factors; C407737:Neurog3 protein, mouse; C489990:Sox4 protein, mouse
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