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Gene Review

Ptf1a  -  pancreas specific transcription factor, 1a

Mus musculus

Synonyms: PTF1-p48, PTF1p48, Pancreas transcription factor 1 subunit alpha, Pancreas-specific transcription factor 1a, Ptf1p48, ...
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Disease relevance of Ptf1a

  • Mutations in the human and mouse PTF1A/Ptf1a genes result in permanent diabetes mellitus and cerebellar agenesis [1].
  • Inactivation of Ptf1a leads to a fate-switch in these precursors that causes them to adopt a ganglion cell fate [2].

High impact information on Ptf1a

  • These experiments provide evidence that Ptf1a expression is specifically connected to the acquisition of pancreatic fate by undifferentiated foregut endoderm [3].
  • We used recombination-based lineage tracing in vivo to show that Ptf1a (also known as PTF1-p48) is expressed at these early stages in the progenitors of pancreatic ducts, exocrine and endocrine cells, rather than being an exocrine-specific gene as previously described [3].
  • Moreover, inactivation of Ptf1a switches the character of pancreatic progenitors such that their progeny proliferate in and adopt the normal fates of duodenal epithelium, including its stem-cell compartment [3].
  • However, at later developmental times, Ascl1 controls the expression of Ptf1a in dIL(A) progenitors to promote inhibitory neuron differentiation while at the same time upregulating Notch signaling to ensure the proper generation of dIL(B) excitatory neurons [4].
  • Furthermore, analysis of Hes1/Ptf1a double mutants revealed that ectopic Ptf1a-cre lineage-labeled cells adopted the fate of region-appropriate gut epithelium or endocrine cells similarly to Ptf1a-inactivated cells in the native pancreatic buds [5].

Biological context of Ptf1a

  • Cerebellar GABAergic progenitors adopt an external granule cell-like phenotype in the absence of Ptf1a transcription factor expression [6].

Anatomical context of Ptf1a

  • Introduction of Ptf1a into glutamatergic neuron precursors in the dorsal telencephalon generated GABAergic neurons with representative morphological and migratory features [7].
  • We show that inactivation of Hes1 induces misexpression of Ptf1a in discrete regions of the primitive stomach and duodenum and throughout the common bile duct [5].
  • Thus, endothelial cell interactions specifically promote early dorsal pancreatic development, at least in part, by inducing Ptf1a(+) pancreatic progenitors [8].
  • These findings indicate that Ptf1a is necessary for the specification and normal production of PCs and cerebellar interneurons [6].
  • We report in this study that, in the cerebellum, the pancreatic transcription factor Ptf1a is required for the specific generation of Purkinje cells (PCs) and interneurons [6].

Regulatory relationships of Ptf1a


Other interactions of Ptf1a

  • We identified the responsible gene, Ptf1a, whose expression was lost in the cerebellar VZ but was maintained in the pancreas in cerebelless [7].
  • Furthermore, we identify Ptf1a as a primary downstream target for Foxn4, a forkhead transcription factor involved in the genesis of horizontal and amacrine neurons [2].
  • E15.5 GR(null/null) mutants were indistinguishable from wild-type regarding pancreatic size, tissue structure and organisation, beta cell fraction and production of exocrine transcription factor Ptf1a, neurogenin 3 and Pdx-1 [9].


  1. Ptf1a determines GABAergic over glutamatergic neuronal cell fate in the spinal cord dorsal horn. Glasgow, S.M., Henke, R.M., Macdonald, R.J., Wright, C.V., Johnson, J.E. Development (2005) [Pubmed]
  2. Ptf1a determines horizontal and amacrine cell fates during mouse retinal development. Fujitani, Y., Fujitani, S., Luo, H., Qiu, F., Burlison, J., Long, Q., Kawaguchi, Y., Edlund, H., Macdonald, R.J., Furukawa, T., Fujikado, T., Magnuson, M.A., Xiang, M., Wright, C.V. Development (2006) [Pubmed]
  3. The role of the transcriptional regulator Ptf1a in converting intestinal to pancreatic progenitors. Kawaguchi, Y., Cooper, B., Gannon, M., Ray, M., MacDonald, R.J., Wright, C.V. Nat. Genet. (2002) [Pubmed]
  4. Ascl1 and Gsh1/2 control inhibitory and excitatory cell fate in spinal sensory interneurons. Mizuguchi, R., Kriks, S., Cordes, R., Gossler, A., Ma, Q., Goulding, M. Nat. Neurosci. (2006) [Pubmed]
  5. Ectopic pancreas formation in Hes1 -knockout mice reveals plasticity of endodermal progenitors of the gut, bile duct, and pancreas. Fukuda, A., Kawaguchi, Y., Furuyama, K., Kodama, S., Horiguchi, M., Kuhara, T., Koizumi, M., Boyer, D.F., Fujimoto, K., Doi, R., Kageyama, R., Wright, C.V., Chiba, T. J. Clin. Invest. (2006) [Pubmed]
  6. Cerebellar GABAergic progenitors adopt an external granule cell-like phenotype in the absence of Ptf1a transcription factor expression. Pascual, M., Abasolo, I., Mingorance-Le Meur, A., Martínez, A., Del Rio, J.A., Wright, C.V., Real, F.X., Soriano, E. Proc. Natl. Acad. Sci. U.S.A. (2007) [Pubmed]
  7. Ptf1a, a bHLH transcriptional gene, defines GABAergic neuronal fates in cerebellum. Hoshino, M., Nakamura, S., Mori, K., Kawauchi, T., Terao, M., Nishimura, Y.V., Fukuda, A., Fuse, T., Matsuo, N., Sone, M., Watanabe, M., Bito, H., Terashima, T., Wright, C.V., Kawaguchi, Y., Nakao, K., Nabeshima, Y. Neuron (2005) [Pubmed]
  8. Endothelial cell interactions initiate dorsal pancreas development by selectively inducing the transcription factor Ptf1a. Yoshitomi, H., Zaret, K.S. Development (2004) [Pubmed]
  9. Glucocorticoid signalling affects pancreatic development through both direct and indirect effects. Gesina, E., Blondeau, B., Milet, A., Le Nin, I., Duchene, B., Czernichow, P., Scharfmann, R., Tronche, F., Breant, B. Diabetologia (2006) [Pubmed]
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