Genetic evidence that Nkx2.2 acts primarily downstream of Neurog3 in pancreatic endocrine lineage development

Many pancreatic transcription factors that are essential for islet cell differentiation have been well characterized; however, because they are often expressed in several different cell populations, their functional hierarchy remains unclear. To parse out the spatiotemporal regulation of islet cell differentiation, we used a Neurog3-Cre allele to ablate Nkx2.2, one of the earliest and most broadly expressed islet transcription factors, specifically in the Neurog3+ endocrine progenitor lineage (Nkx2.2△endo). Remarkably, many essential components of the β cell transcriptional network that were down-regulated in the Nkx2.2KO mice, were maintained in the Nkx2.2△endo mice - yet the Nkx2.2△endo mice displayed…

• CN
  Consejo Nacional de Ciencia y Tecnología
• NI
  National Institute of General Medical Sciences

  Award: Graduate student training grant, T32GM007088
• NI
  National Institute of Diabetes and Digestive and Kidney Diseases

  Awards: R01 DK082590, Graduate student training grant, T32DK007328, NRSA individual predoctoral award, F31 DK107028