Pdx-1 and Ptf1a concurrently determine fate specification of pancreatic multipotent progenitor cells.

Burlison JS, Long Q, Fujitani Y, Wright CV, Magnuson MA
Dev Biol. 2008 316 (1): 74-86

PMID: 18294628 · PMCID: PMC2425677 · DOI:10.1016/j.ydbio.2008.01.011

The pancreas is derived from a pool of multipotent progenitor cells (MPCs) that co-express Pdx-1 and Ptf1a. To more precisely define how the individual and combined loss of Pdx-1 and Ptf1a affects pancreatic MPC specification and differentiation we derived and studied mice bearing a novel Ptf1a(YFP) allele. While the expression of Pdx-1 and Ptf1a in pancreatic MPCs coincides between E9.5 and 12.5 the developmental phenotypes of Pdx-1 null and Pdx-1; Ptf1a double null mice are indistinguishable, and an early pancreatic bud is formed in both cases. This finding indicates that Pdx-1 is required in the foregut endoderm prior to Ptf1a for pancreatic MPC specification. We also found that Ptf1a is neither required for specification of Ngn3-positive endocrine progenitors nor differentiation of mature beta-cells. In the absence of Pdx-1 Ngn3-positive cells were not observed after E9.5. Thus, in contrast to the deletion of Ptf1a, the loss of Pdx-1 precludes the sustained Ngn3-based derivation of endocrine progenitors from pancreatic MPCs. Taken together, these studies indicate that Pdx-1 and Ptf1a have distinct but interdependent functions during pancreatic MPC specification.

MeSH Terms (16)

Alleles Animals Basic Helix-Loop-Helix Transcription Factors Cell Differentiation Embryonic Stem Cells Homeodomain Proteins Islets of Langerhans Luminescent Proteins Mice Mice, Mutant Strains Microscopy, Fluorescence Multipotent Stem Cells Nerve Tissue Proteins Pancreas Trans-Activators Transcription Factors

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