The concerted activities of Pax4 and Nkx2.2 are essential to initiate pancreatic β-cell differentiation

Junfeng Wang, Lynda Elghazi, Susan E. Parker, Hasan Kizilocak, Masahide Asano, Lori Sussel, Beatriz Sosa-Pineda*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

121 Scopus citations

Abstract

Pancreatic β cells play a central role in maintaining glucose homeostasis because they secrete insulin in response to increased level of blood glucose; failure of this capacity constitutes a major component of the pathogenesis of diabetes. The identification of key regulators of pancreatic β-cell differentiation is relevant for the overall understanding of this process and for future experiments aimed at regenerating insulin-producing β cells from pancreatic or embryonic stem cells. Several studies using transgenic or knockout mice have established that the development and function of pancreatic β cells are controlled by several genes encoding specific transcription factors. By inactivating the homeobox gene Pax4, we previously demonstrated that its function is required for the formation of mature insulin-producing cells. Here, we show that during pancreas ontogeny, Pax4 is expressed in differentiating endocrine cells, including β cells. Pax4 activity appears essential for appropriate initiation of β-cell differentiation because loss of Pax4 prevents the expression of Pdx1, HB9 and insulin in β-cell precursors. This role of Pax4 appears to be accomplished via its genetic interaction with another homeobox gene, Nkx2.2.

Original languageEnglish (US)
Pages (from-to)178-189
Number of pages12
JournalDevelopmental Biology
Volume266
Issue number1
DOIs
StatePublished - Feb 1 2004

Keywords

  • Mouse
  • Nkx2.2
  • Pancreas
  • Pax4
  • Pax6
  • β-cell differentiation

ASJC Scopus subject areas

  • Molecular Biology
  • Developmental Biology
  • Cell Biology

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