Genomes and Genes
Gene Symbol: Ptf1a
Description: pancreas specific transcription factor, 1a
Alias: PTF1-p48, PTF1p48, bHLHa29, pancreas transcription factor 1 subunit alpha, bHLH transcription factor p48, p48 DNA-binding subunit of transcription factor PTF1, pancreas transcription factor1 p48 subunit
- Haumaitre C, Barbacci E, Jenny M, Ott M, Gradwohl G, Cereghini S. Lack of TCF2/vHNF1 in mice leads to pancreas agenesis. Proc Natl Acad Sci U S A. 2005;102:1490-5 pubmed..factors Ipf1 and Hlxb9 but lacks the key transcription factor involved in the acquisition of a pancreatic fate, Ptf1a, as well as all endocrine precursor cells...
- Pylayeva Gupta Y, Lee K, Hajdu C, Miller G, Bar Sagi D. Oncogenic Kras-induced GM-CSF production promotes the development of pancreatic neoplasia. Cancer Cell. 2012;21:836-47 pubmed publisher..These results identify a pathway that links oncogenic activation to the evasion of antitumor immunity. ..
- Fujitani Y, Fujitani S, Boyer D, Gannon M, Kawaguchi Y, Ray M, et al. Targeted deletion of a cis-regulatory region reveals differential gene dosage requirements for Pdx1 in foregut organ differentiation and pancreas formation. Genes Dev. 2006;20:253-66 pubmed
- Apelqvist A, Li H, Sommer L, Beatus P, Anderson D, Honjo T, et al. Notch signalling controls pancreatic cell differentiation. Nature. 1999;400:877-81 pubmed..These data provide evidence that ngn3 acts as proendocrine gene and that Notch signalling is critical for the decision between the endocrine and progenitor/exocrine fates in the developing pancreas. ..
- Connolly M, Mallen St Clair J, Bedrosian A, Malhotra A, Vera V, Ibrahim J, et al. Distinct populations of metastases-enabling myeloid cells expand in the liver of mice harboring invasive and preinvasive intra-abdominal tumor. J Leukoc Biol. 2010;87:713-25 pubmed publisher..These findings may explain the propensity of patients with intra-abdominal cancers to develop liver metastases and suggest a promising target for experimental therapeutics. ..
- Fukuda A, Kawaguchi Y, Furuyama K, Kodama S, Horiguchi M, Kuhara T, et al. Reduction of Ptf1a gene dosage causes pancreatic hypoplasia and diabetes in mice. Diabetes. 2008;57:2421-31 pubmed publisherMost pancreatic endocrine cells derive from Ptf1a-expressing progenitor cells. In humans, nonsense mutations in Ptf1a have recently been identified as a cause of permanent neonatal diabetes associated with pancreatic agenesis...
- Miyatsuka T, Matsuoka T, Shiraiwa T, Yamamoto T, Kojima I, Kaneto H. Ptf1a and RBP-J cooperate in activating Pdx1 gene expression through binding to Area III. Biochem Biophys Res Commun. 2007;362:905-9 pubmed..Pdx1 and Ptf1a are expressed in pancreatic progenitor cells, which give rise to all three types of pancreatic tissue...
- Meredith D, Masui T, Swift G, Macdonald R, Johnson J. Multiple transcriptional mechanisms control Ptf1a levels during neural development including autoregulation by the PTF1-J complex. J Neurosci. 2009;29:11139-48 pubmed publisherb>Ptf1a, along with an E protein and Rbpj, forms the transcription factor complex PTF1-J that is essential for proper specification of inhibitory neurons in the spinal cord, retina, and cerebellum...
- Mazur P, Einwächter H, Lee M, Sipos B, Nakhai H, Rad R, et al. Notch2 is required for progression of pancreatic intraepithelial neoplasia and development of pancreatic ductal adenocarcinoma. Proc Natl Acad Sci U S A. 2010;107:13438-43 pubmed publisher..Our study supports the concept of distinctive roles of individual Notch receptors in cancer development. ..
- Masui T, Long Q, Beres T, Magnuson M, Macdonald R. Early pancreatic development requires the vertebrate Suppressor of Hairless (RBPJ) in the PTF1 bHLH complex. Genes Dev. 2007;21:2629-43 pubmedb>PTF1a is an unusual basic helix-loop-helix (bHLH) transcription factor that is required for the development of the pancreas...
- Komine O, Nagaoka M, Hiraoka Y, Hoshino M, Kawaguchi Y, Pear W, et al. RBP-J promotes the maturation of neuronal progenitors. Dev Biol. 2011;354:44-54 pubmed publisher..This study shows a novel RBP-J function that promotes INP differentiation. ..
- Rose S, Swift G, Peyton M, Hammer R, MacDonald R. The role of PTF1-P48 in pancreatic acinar gene expression. J Biol Chem. 2001;276:44018-26 pubmed..Comparison of the 5'-gene flanking regions of the mouse, rat, and human genes identified conserved sequence blocks containing binding sites for known gut transcription factors within the acinar cell-specific control region. ..
- Kilic G, Wang J, Sosa Pineda B. Osteopontin is a novel marker of pancreatic ductal tissues and of undifferentiated pancreatic precursors in mice. Dev Dyn. 2006;235:1659-67 pubmed..Finally, the maintenance of Opn expression in pancreatic tissues of adults argues for a possible function of this protein in injury and pathologic responses. ..
- Shi G, Zhu L, Sun Y, Bettencourt R, Damsz B, Hruban R, et al. Loss of the acinar-restricted transcription factor Mist1 accelerates Kras-induced pancreatic intraepithelial neoplasia. Gastroenterology. 2009;136:1368-78 pubmed publisher..We propose that convergence of EGFR, Notch, and Kras pathways in acinar cells lacking Mist1 leads to enhanced mPanIN formation. ..
- Mukherjee P, Basu G, Tinder T, Subramani D, Bradley J, Arefayene M, et al. Progression of pancreatic adenocarcinoma is significantly impeded with a combination of vaccine and COX-2 inhibition. J Immunol. 2009;182:216-24 pubmed..The preclinical data provide the rationale to design clinical trials with a combination of MUC1-based vaccine, celecoxib, and gemcitabine for the treatment of pancreatic cancer...
- CLARK C, Hingorani S, Mick R, Combs C, Tuveson D, Vonderheide R. Dynamics of the immune reaction to pancreatic cancer from inception to invasion. Cancer Res. 2007;67:9518-27 pubmed..Efforts to test potent inhibitors of MDSC, tumor-associated macrophages, and Treg, particularly early in the disease represent important next steps for developing novel immunotherapy of cancer. ..
- Pan F, Bankaitis E, Boyer D, Xu X, Van De Casteele M, Magnuson M, et al. Spatiotemporal patterns of multipotentiality in Ptf1a-expressing cells during pancreas organogenesis and injury-induced facultative restoration. Development. 2013;140:751-64 pubmed publisher..We used inducible lineage-tracing from the MPC-instructive gene Ptf1a to define systematically in mice the switch of Ptf1a(+) MPCs to unipotent proacinar competence during the ..
- Poche R, Kwan K, Raven M, Furuta Y, Reese B, Behringer R. Lim1 is essential for the correct laminar positioning of retinal horizontal cells. J Neurosci. 2007;27:14099-107 pubmed..This study is the first to describe a cell type-specific genetic program that is essential for targeting a discrete retinal neuron population to the proper lamina. ..
- Mizuguchi R, Kriks S, Cordes R, Gossler A, Ma Q, Goulding M. Ascl1 and Gsh1/2 control inhibitory and excitatory cell fate in spinal sensory interneurons. Nat Neurosci. 2006;9:770-8 pubmed..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 ..
- Murtaugh L, Law A, Dor Y, Melton D. Beta-catenin is essential for pancreatic acinar but not islet development. Development. 2005;132:4663-74 pubmed..Thus, our data are consistent with a crucial role for canonical Wnt signals in acinar lineage specification and differentiation. ..
- Norgaard G, Jensen J, Jensen J. FGF10 signaling maintains the pancreatic progenitor cell state revealing a novel role of Notch in organ development. Dev Biol. 2003;264:323-38 pubmed..These data suggest that FGF10 signaling serves to integrate cell growth and terminal differentiation at the level of Notch activation, revealing a novel second role of this key signaling system during pancreatic development. ..
- Masui T, Swift G, Hale M, Meredith D, Johnson J, Macdonald R. Transcriptional autoregulation controls pancreatic Ptf1a expression during development and adulthood. Mol Cell Biol. 2008;28:5458-68 pubmed publisherThe basic helix-loop-helix (bHLH) transcription factor PTF1a is critical to the development of the embryonic pancreas...
- Hori K, Cholewa Waclaw J, Nakada Y, Glasgow S, Masui T, Henke R, et al. A nonclassical bHLH Rbpj transcription factor complex is required for specification of GABAergic neurons independent of Notch signaling. Genes Dev. 2008;22:166-78 pubmed publisher..The basic helix-loop-helix (bHLH) transcription factor Ptf1a is essential for the generation of GABAergic inhibitory neurons in the dorsal spinal cord, cerebellum, and retina...
- Liu Y, MacDonald R, Swift G. DNA binding and transcriptional activation by a PDX1.PBX1b.MEIS2b trimer and cooperation with a pancreas-specific basic helix-loop-helix complex. J Biol Chem. 2001;276:17985-93 pubmed..PBX1b.MEIS2b complex cooperates with the PTF1 basic helix-loop-helix complex to activate an ELA1 minienhancer in HeLa cells and that this cooperation requires all three homeoprotein subunits, including the PDX1 activation domain. ..
- Glasgow S, Henke R, Macdonald R, Wright C, Johnson J. Ptf1a determines GABAergic over glutamatergic neuronal cell fate in the spinal cord dorsal horn. Development. 2005;132:5461-9 pubmedMutations in the human and mouse PTF1A/Ptf1a genes result in permanent diabetes mellitus and cerebellar agenesis. We show that Ptf1a is present in precursors to GABAergic neurons in spinal cord dorsal horn as well as the cerebellum...
- Gradwohl G, Dierich A, LeMeur M, Guillemot F. neurogenin3 is required for the development of the four endocrine cell lineages of the pancreas. Proc Natl Acad Sci U S A. 2000;97:1607-11 pubmed..Thus, ngn3 is required for the specification of a common precursor for the four pancreatic endocrine cell types. ..
- Thompson N, Gesina E, Scheinert P, Bucher P, Grapin Botton A. RNA profiling and chromatin immunoprecipitation-sequencing reveal that PTF1a stabilizes pancreas progenitor identity via the control of MNX1/HLXB9 and a network of other transcription factors. Mol Cell Biol. 2012;32:1189-99 pubmed publisher..Among those factors, PTF1a, a basic helix-loop-helix (bHLH) transcription factor which controls pancreas exocrine cell differentiation, ..
- Collins M, Bednar F, Zhang Y, Brisset J, Galban S, Galban C, et al. Oncogenic Kras is required for both the initiation and maintenance of pancreatic cancer in mice. J Clin Invest. 2012;122:639-53 pubmed publisher..They also strongly support the notion that inhibiting KrasG12D, or its downstream effectors, could provide a new approach for the treatment of pancreatic cancer. ..
- Pulkkinen M, Spencer Dene B, Dickson C, Otonkoski T. The IIIb isoform of fibroblast growth factor receptor 2 is required for proper growth and branching of pancreatic ductal epithelium but not for differentiation of exocrine or endocrine cells. Mech Dev. 2003;120:167-75 pubmed..Our results thus suggest that Fgfr2b-mediated signaling plays a major role in pancreatic ductal proliferation and branching morphogenesis, but has little effect on endocrine and exocrine differentiation. ..
- Laconti J, Shivapurkar N, Preet A, Deslattes Mays A, Peran I, Kim S, et al. Tissue and serum microRNAs in the Kras(G12D) transgenic animal model and in patients with pancreatic cancer. PLoS ONE. 2011;6:e20687 pubmed publisher..These findings support the significance of detecting miRs in the circulation and suggests that circulating miRs could serve as indicators of drug response. ..
- Ardito C, Grüner B, Takeuchi K, Lubeseder Martellato C, Teichmann N, Mazur P, et al. EGF receptor is required for KRAS-induced pancreatic tumorigenesis. Cancer Cell. 2012;22:304-17 pubmed publisher..Without EGFR activity, active RAS levels are not sufficient to induce robust MEK/ERK activity, a requirement for epithelial transformation...
- Qiu F, Jiang H, Xiang M. A comprehensive negative regulatory program controlled by Brn3b to ensure ganglion cell specification from multipotential retinal precursors. J Neurosci. 2008;28:3392-403 pubmed publisher..Our data suggest that Brn3b specifies the RGC fate from multipotential precursors not only by promoting RGC differentiation but also by suppressing non-RGC differentiation programs as a safeguard mechanism. ..
- Henke R, Savage T, Meredith D, Glasgow S, Hori K, Dumas J, et al. Neurog2 is a direct downstream target of the Ptf1a-Rbpj transcription complex in dorsal spinal cord. Development. 2009;136:2945-54 pubmed publisher..Although the components of PTF1-J have been identified as the basic helix-loop-helix (bHLH) factor Ptf1a, its heterodimeric E-protein partner, and Rbpj, no neural targets are known for this transcription factor complex...
- Martin M, Gallego Llamas J, Ribes V, Kedinger M, Niederreither K, Chambon P, et al. Dorsal pancreas agenesis in retinoic acid-deficient Raldh2 mutant mice. Dev Biol. 2005;284:399-411 pubmed..We conclude that RA synthesized in the mesenchyme is specifically required for the normal development of the dorsal pancreatic endoderm at a stage preceding Pdx 1 function. ..
- Ying H, Kimmelman A, Lyssiotis C, Hua S, Chu G, Fletcher Sananikone E, et al. Oncogenic Kras maintains pancreatic tumors through regulation of anabolic glucose metabolism. Cell. 2012;149:656-70 pubmed publisher..Together, this work provides in vivo mechanistic insights into how oncogenic Kras promotes metabolic reprogramming in native tumors and illuminates potential metabolic targets that can be exploited for therapeutic benefit in PDAC. ..
- Kawaguchi Y, Cooper B, Gannon M, Ray M, Macdonald R, Wright C. The role of the transcriptional regulator Ptf1a in converting intestinal to pancreatic progenitors. Nat Genet. 2002;32:128-34 pubmed..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 ..
- Besmer D, Curry J, Roy L, Tinder T, Sahraei M, Schettini J, et al. Pancreatic ductal adenocarcinoma mice lacking mucin 1 have a profound defect in tumor growth and metastasis. Cancer Res. 2011;71:4432-42 pubmed publisher..This is the first study to utilize a Muc1-null PDA mouse to fully elucidate the oncogenic role of MUC1, both in vivo and in vitro. ..
- Tinder T, Subramani D, Basu G, Bradley J, Schettini J, Million A, et al. MUC1 enhances tumor progression and contributes toward immunosuppression in a mouse model of spontaneous pancreatic adenocarcinoma. J Immunol. 2008;181:3116-25 pubmed..Thus, the mouse model is ideally suited for testing novel chemopreventive and therapeutic strategies against pancreatic cancer. ..
- Hoshino M, Nakamura S, Mori K, Kawauchi T, Terao M, Nishimura Y, et al. Ptf1a, a bHLH transcriptional gene, defines GABAergic neuronal fates in cerebellum. Neuron. 2005;47:201-13 pubmed..We identified the responsible gene, Ptf1a, whose expression was lost in the cerebellar VZ but was maintained in the pancreas in cerebelless...
- Papadopoulou S, Edlund H. Attenuated Wnt signaling perturbs pancreatic growth but not pancreatic function. Diabetes. 2005;54:2844-51 pubmed..Collectively, our data provide evidence that Wnt signaling is required for pancreatic growth but not adult beta-cell function. ..
- Zhu L, Shi G, Schmidt C, Hruban R, Konieczny S. Acinar cells contribute to the molecular heterogeneity of pancreatic intraepithelial neoplasia. Am J Pathol. 2007;171:263-73 pubmed..Identification of an acinar contribution to PanIN formation offers new directions for successful targeted therapeutic approaches to combat this disease. ..
- Pascual M, Abasolo I, Mingorance Le Meur A, MARTINEZ A, Del Río J, Wright C, et al. Cerebellar GABAergic progenitors adopt an external granule cell-like phenotype in the absence of Ptf1a transcription factor expression. Proc Natl Acad Sci U S A. 2007;104:5193-8 pubmedWe 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...
- Hingorani S, Petricoin E, Maitra A, Rajapakse V, King C, Jacobetz M, et al. Preinvasive and invasive ductal pancreatic cancer and its early detection in the mouse. Cancer Cell. 2003;4:437-50 pubmed..Finally, mice with PanINs have an identifiable serum proteomic signature, suggesting a means of detecting the preinvasive state in patients. ..
- Esni F, Ghosh B, Biankin A, Lin J, Albert M, Yu X, et al. Notch inhibits Ptf1 function and acinar cell differentiation in developing mouse and zebrafish pancreas. Development. 2004;131:4213-24 pubmed..These results define a normal inhibitory role for Notch in the regulation of exocrine pancreatic differentiation. ..
- Betley J, Wright C, Kawaguchi Y, Erdelyi F, Szabo G, Jessell T, et al. Stringent specificity in the construction of a GABAergic presynaptic inhibitory circuit. Cell. 2009;139:161-74 pubmed publisher..The organization of a GABAergic circuit that mediates presynaptic inhibition in the mammalian CNS is therefore controlled by a stringent program of sensory recognition and signaling. ..
- Chiang M, Melton D. Single-cell transcript analysis of pancreas development. Dev Cell. 2003;4:383-93 pubmed..This form of single-cell transcriptional analysis can be applied to any developmental process or tissue to characterize distinct cell types. ..
- Krapp A, Knöfler M, Frutiger S, Hughes G, Hagenbuchle O, Wellauer P. The p48 DNA-binding subunit of transcription factor PTF1 is a new exocrine pancreas-specific basic helix-loop-helix protein. EMBO J. 1996;15:4317-29 pubmed..Thus the pancreas-specific DNA-binding activity of PTF1 originates from the synthesis of at least one cell-specific component rather than from a cell-specific assembly of more widely distributed proteins. ..
- Siveke J, Einwächter H, Sipos B, Lubeseder Martellato C, Kloppel G, Schmid R. Concomitant pancreatic activation of Kras(G12D) and Tgfa results in cystic papillary neoplasms reminiscent of human IPMN. Cancer Cell. 2007;12:266-79 pubmed..In conclusion, Egfr signaling in synergy with oncogenic Kras may be a prerequisite for IPMN development and progression to pancreatic cancer. ..
- Aguilera K, Rivera L, Hur H, Carbon J, Toombs J, Goldstein C, et al. Collagen signaling enhances tumor progression after anti-VEGF therapy in a murine model of pancreatic ductal adenocarcinoma. Cancer Res. 2014;74:1032-44 pubmed publisher..Together, these findings suggest that collagen actively promotes PDA spread and that enhanced disease progression associated with anti-VEGF therapy can arise from elevated extracellular matrix-mediated signaling. ..
- Obata J, Yano M, Mimura H, Goto T, Nakayama R, Mibu Y, et al. p48 subunit of mouse PTF1 binds to RBP-Jkappa/CBF-1, the intracellular mediator of Notch signalling, and is expressed in the neural tube of early stage embryos. Genes Cells. 2001;6:345-60 pubmed..We isolated PTF1 p48 from 9.5-day mouse embryos as a binding protein of RBP-Jkappa, a mediator of Notch signalling...
- Krapp A, Knöfler M, Ledermann B, Burki K, Berney C, Zoerkler N, et al. The bHLH protein PTF1-p48 is essential for the formation of the exocrine and the correct spatial organization of the endocrine pancreas. Genes Dev. 1998;12:3752-63 pubmed
- Mohammed A, Janakiram N, Li Q, Madka V, Ely M, Lightfoot S, et al. The epidermal growth factor receptor inhibitor gefitinib prevents the progression of pancreatic lesions to carcinoma in a conditional LSL-KrasG12D/+ transgenic mouse model. Cancer Prev Res (Phila). 2010;3:1417-26 pubmed publisher..The present study highlights the promise of chemoprevention and the potential usefulness of EGFR inhibitors in individuals at high risk for pancreatic cancer. ..
- Soyer J, Flasse L, Raffelsberger W, Beucher A, Orvain C, Peers B, et al. Rfx6 is an Ngn3-dependent winged helix transcription factor required for pancreatic islet cell development. Development. 2010;137:203-12 pubmed publisher..By contrast, beta cells, whose number is only slightly reduced, were no longer clustered in a compact islet. These data unveil Rfx6 as a novel regulator of islet cell development. ..
- Hart A, Papadopoulou S, Edlund H. Fgf10 maintains notch activation, stimulates proliferation, and blocks differentiation of pancreatic epithelial cells. Dev Dyn. 2003;228:185-93 pubmed..Together, our data suggest a role for FGF10/FGFR2b signalling in regulation of pancreatic cell proliferation and differentiation and that FGF10/FGFR2b signalling affects the Notch-mediated lateral inhibition pathway. ..
- Beres T, Masui T, Swift G, Shi L, Henke R, Macdonald R. PTF1 is an organ-specific and Notch-independent basic helix-loop-helix complex containing the mammalian Suppressor of Hairless (RBP-J) or its paralogue, RBP-L. Mol Cell Biol. 2006;26:117-30 pubmed..It comprises a dimer of P48/PTF1a (a pancreas and neural restricted basic helix-loop-helix [bHLH] protein) and a class A bHLH protein, together with ..
- Izeradjene K, Combs C, Best M, Gopinathan A, Wagner A, Grady W, et al. Kras(G12D) and Smad4/Dpc4 haploinsufficiency cooperate to induce mucinous cystic neoplasms and invasive adenocarcinoma of the pancreas. Cancer Cell. 2007;11:229-43 pubmed..Our findings suggest that the sequence, as well as the context, in which these critical mutations are acquired helps determine the ensuing pathology. ..
- Nakhai H, Sel S, Favor J, Mendoza Torres L, Paulsen F, Duncker G, et al. Ptf1a is essential for the differentiation of GABAergic and glycinergic amacrine cells and horizontal cells in the mouse retina. Development. 2007;134:1151-60 pubmed..We report here that the tissue-specific bHLH transcription factor Ptf1a (also known as PTF1-p48) is expressed from embryonic day 12.5 of gestation (E12...
- Fukuda A, Wang S, Morris J, Folias A, Liou A, Kim G, et al. Stat3 and MMP7 contribute to pancreatic ductal adenocarcinoma initiation and progression. Cancer Cell. 2011;19:441-55 pubmed publisher..Finally, we demonstrate that serum MMP7 level in human patients with PDA correlated with metastatic disease and survival. ..
- Schaffer A, Freude K, Nelson S, Sander M. Nkx6 transcription factors and Ptf1a function as antagonistic lineage determinants in multipotent pancreatic progenitors. Dev Cell. 2010;18:1022-9 pubmed publisher..1/Nkx6.2 (Nkx6) and Ptf1a. Using genetic loss- and gain-of-function approaches, we demonstrate that Nkx6 factors and Ptf1a are required and ..
- Yamada M, Terao M, Terashima T, Fujiyama T, Kawaguchi Y, Nabeshima Y, et al. Origin of climbing fiber neurons and their developmental dependence on Ptf1a. J Neurosci. 2007;27:10924-34 pubmed..Here, we describe the origin of the CF neuron lineage and the involvement of Ptf1a (pancreatic transcription factor 1a) in CF neuron development...
- Fujitani Y, Fujitani S, Luo H, Qiu F, Burlison J, Long Q, et al. Ptf1a determines horizontal and amacrine cell fates during mouse retinal development. Development. 2006;133:4439-50 pubmed..We report that Ptf1a, a basic-helix-loop-helix (bHLH) transcription factor, is transiently expressed by post-mitotic precursors in the ..