Pdx-1 and Ptf1a concurrently determine fate specification of pancreatic multipotent progenitor cells.
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.
Burlison
Jared S
JS
Center for Stem Cell Biology, Vanderbilt University School of Medicine, Nashville, TN 37232-0225, USA.
Long
Qiaoming
Q
Fujitani
Yoshio
Y
Wright
Christopher V E
CV
Magnuson
Mark A
MA
D000483:Alleles; D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins / Q000502:physiology; D002454:Cell Differentiation; D053595:Embryonic Stem Cells / Q000166:cytology / Q000378:metabolism; D018398:Homeodomain Proteins / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D007515:Islets of Langerhans / Q000166:cytology / Q000196:embryology / Q000378:metabolism; D008164:Luminescent Proteins / Q000032:analysis / Q000235:genetics; D051379:Mice; D008817:Mice, Mutant Strains; D008856:Microscopy, Fluorescence; D039902:Multipotent Stem Cells / Q000166:cytology* / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000502:physiology; D010179:Pancreas / Q000166:cytology / Q000196:embryology* / Q000378:metabolism; D015534:Trans-Activators / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D014157:Transcription Factors / Q000032:analysis / Q000235:genetics / Q000378:metabolism*
D051792:Basic Helix-Loop-Helix Proteins; D018398:Homeodomain Proteins; D008164:Luminescent Proteins; D009419:Nerve Tissue Proteins; D015534:Trans-Activators; D014157:Transcription Factors; C407737:Neurog3 protein, mouse; C084010:pancreatic and duodenal homeobox 1 protein; C062602:transcription factor PTF1