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The role of the transcriptional regulator Ptf1a in converting intestinal to pancreatic progenitors
Abstract
Pancreas development begins with the formation of buds at specific sites in the embryonic foregut endoderm. 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. 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. Consistent with the proposal that Ptf1a supports the specification of precursors of all three pancreatic cell types, transgene-based expression of Pdx1, a gene essential to pancreas formation, from Ptf1a cis-regulatory sequences restores pancreas tissue to Pdx1-null mice that otherwise lack mature exocrine and endocrine cells because of an early arrest in organogenesis. These experiments provide evidence that Ptf1a expression is specifically connected to the acquisition of pancreatic fate by undifferentiated foregut endoderm.
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“Specific recombination in epithelial cells of the pancreas was confirmed by immunohistochemical stainings for tdRFP in Ptf1aCre/+ [35] x LSL-tdRFPKI/KI [55, 56] mice (Additional file 1: Fig. S3d) [56].”
From TBX3 is dynamically expressed in pancreatic organogenesis and fine-tunes regeneration (2023) · cites this paper as [35]
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Misexpression of Ptf1a in Cortical Pyramidal CellsIn VivoPromotes an Inhibitory Peptidergic Identity
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“Ptf1aCre mice (Kawaguchi et al., 2002) were used to generate Ptf1a knock-outs, as described previously (Borromeo et al., 2014).”
MethodHosokawa, S., Furuyama, K., Horiguchi, M., Aoyama, Y., Tsuboi, K., Sakikubo, M., Goto, T., Hirata, K., Tanabe, W., Nakano, Y., et al. (2015) · Scientific Reports · doi:10.1038/srep08518 · Cited by 8
Self-citationSources of β-cells for human cell-based therapies for diabetes
Itkin-Ansari, P., & Levine, F. (2007) · Cell Biochemistry and Biophysics · doi:10.1385/cbb:40:3:109 · Cited by 8
“endocrine cells than previously thought (27) and might have the ability to alter their differentiation state to become endocrine cells.”
Kanno, R., Ogihara, T., Igarashi, Y., Tanaka, Y., Smith, S. B., Kojima, I., German, M., Kawamori, R., & Watada, H. (2006) · Biochimica et Biophysica Acta · doi:10.1016/j.bbaexp.2006.01.004 · Cited by 8
Lin, J. W., Biankin, A., Horb, M. E., Ghosh, B., Prasad, N., Yee, N., Pack, M., & Leach, S. (2004) · Developmental Biology · doi:10.1016/j.ydbio.2004.07.001 · Cited by 8
Horiguchi, M., Yoshida, M., Hirata, K., Furuyama, K., Masui, T., Uemoto, S., & Kawaguchi, Y. (2019) · FEBS Letters · doi:10.1002/1873-3468.13504 · Cited by 7
Self-citationOntogeny of the spinal cord dorsal horn
Roome, R. B., Yadav, A., Flores, L., Puarr, A. K., Nardini, D., Richardson, A. J. W., Waclaw, R. R., Arkell, R. M., Menon, V., Johnson, J. E. B., et al. (2026) · Science · doi:10.1126/science.adx5781 · Cited by 24
“To remove dorsal inhibitory neurons from the spinal cord, we used Ptf1a Cre/Cre homozygous null embryos, in which the dI4/dILA neurons are trans-fated to become dI5/dILB neurons (29, 55).”
Mousavi, F., Thompson, J. K., Lau, J., Renollet, N. M., Martin, M. B., McGue, J. J., Hassan, O., Frankel, T. L., Shooshtari, P., Pin, C. L., et al. (2024) · Cellular and Molecular Gastroenterology and Hepatology · doi:10.1016/j.jcmgh.2024.101428 · Cited by 6
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Kobayashi, N., Shinohara, H., Haruta, S., Udagawa, H., & Ueno, M. (2021) · Langenbeck's archives of surgery (Print) · doi:10.1007/s00423-021-02337-z · Cited by 7
Tian, J.-Z., Xing, S., Feng, J.-Y., Yang, S.-H., Ding, Y.-F., Huang, X.-T., Yang, J.-S., & Yang, W.-J. (2021) · Scientific Reports · doi:10.1038/s41598-021-92075-5 · Cited by 7
Essential role of Notch/Hes1 signaling in postnatal pancreatic exocrine development
Kuriyama, K., Kodama, Y., Shiokawa, M., Nishikawa, Y., Marui, S., Kuwada, T., Sogabe, Y., Kakiuchi, N., Tomono, T., Matsumori, T., et al. (2021) · Journal of gastroenterology · doi:10.1007/s00535-021-01779-y · Cited by 7
“Experimental animals were generated by crossing Ptf1a ? [1] or Pdx1-Cre [12] (supplied by Y Kawaguchi, Kyoto University, Kyoto, Japan) with Hes1 [13] and/or Rosa26 [6] (supplied by D Melton, Harvard University, MA, USA).”
BackgroundMethodInfluentialMIST1, an Inductive Signal for Salivary Amylase in Mesenchymal Stem Cells
Mona, M., Miller, R. C., Li, H., Park, Y.-J., Zaman, R., Yang, L.-J., & Cha, S. (2019) · International Journal of Molecular Sciences · doi:10.3390/ijms20030767 · Cited by 9
Nardilysin inhibits pancreatitis and suppresses pancreatic ductal adenocarcinoma initiation in mice
Ikuta, K., Fukuda, A., Ogawa, S., Masuo, K., Goto, N., Hiramatsu, Y., Tsuda, M., Kimura, Y., Matsumoto, Y., Kimura, Y., et al. (2018) · Gut · doi:10.1136/gutjnl-2017-315425 · Cited by 7
Miao, Y., Soudy, F. A., Xu, Z., Liao, M., Zhao, S., & Li, X. (2017) · BioMed Research International · doi:10.1155/2017/7132941 · Cited by 7
“Ptf1a gene is the key factor for the fate determination of the pancreatic exocrine cells which is indispensable for pancreas development [43].”
BackgroundRegulating the dorsal neural tube expression of Ptf1a through a distal 3′ enhancer
Mona, B., Avila, J., Meredith, D., Kollipara, R., & Johnson, J. E. (2016) · Developmental Biology · doi:10.1016/j.ydbio.2016.06.033 · Cited by 7
“…regions of the developing CNS including the spinal cord, brainstem, cerebellum, and retina (Dullin et al., 2007; Fujitani et al., 2006; Glasgow et al., 2005; Hoshino et al., 2005; Iskusnykh et al., 2016; Kawaguchi et al., 2002; Millen et al., 2014; Nakhai e, UT Southwestern Medical , United States.”
Coordination of stress signals by the lysine methyltransferase SMYD2 promotes pancreatic cancerPreprint
Reynoird, N., Mazur, P. K., Stellfeld, T., Flores, N. M., Lofgren, S. M., Carlson, S. M., Brambilla, E., Hainaut, P., Kaznowska, E., Arrowsmith, C., et al. (2016) · Genes & Development · doi:10.1101/gad.275529.115 · Cited by 7
“Ptf1a +/ Cre , Kras +/ LSL-G12D , Trp53 loxP/loxP mice have been described before (Jonkers et al. 2001; Kawaguchi et al. 2002; Hingorani et al. 2003).”
Pérez-García, A., Perez-Duran, P., Wossning, T., Sernandez, I. V., Mur, S., Cañamero, M., Real, F., & Ramiro, A. (2015) · EMBO Molecular Medicine · doi:10.15252/emmm.201505348 · Cited by 7
“…cells, we bred R26AID+/KI mice with mice expressing the Cre-recombinase under a villin promoter, which specifically drives expression in colon (el Marjou et al, 2004) (R26AID+/KIVillin-CRE+/TG mice), or the pancreasspecific Ptf1 (p48) gene (Kawaguchi et al, 2002) (R26AID+/KI p48-CRE+/KI mice).”
BackgroundTransdifferentiation of Fibroblasts by Defined Factors
Zhao, Z., Xu, M., Wu, M., Tian, X., Zhang, C., & Fu, X. (2015) · Cellular Reprogramming · doi:10.1089/cell.2014.0089 · Cited by 6
“Kawaguchi’s experiments (Kawaguchi et al., 2002) provide evidence that Ptf1a expression is specifically associated with the determination of pancreatic fate in undifferentiated foregut endoderm.”
BackgroundAn RMCE-derived cyan fluorescent protein reporter allele for Pdx1
Potter, L. A., Choi, E., Hipkens, S., Wright, C. V. E., & Magnuson, M. A. (2012) · Genesis · doi:10.1002/dvg.20804 · Cited by 7
“5 the pancreatic epithelium consists of a heterogeneous population of multipotent progenitor cells (MPCs) that give rise to the endocrine, exocrine, and ductal cell types found in the adult organ (Gu et al., 2002; Kawaguchi et al., 2002; Zhou et al., 2007).”
BackgroundSelf-citationCaveats and considerations for performing pancreas‐specific gene manipulations in the mouse
Magnuson, M. A., & Burlison, J. S. (2007) · Diabetes, obesity and metabolism · doi:10.1111/j.1463-1326.2007.00771.x · Cited by 7
Islet-derived multipotential cells/progenitor cells
Teitelman, G. (2007) · Cell Biochemistry and Biophysics · doi:10.1385/cbb:40:3:89 · Cited by 7
HMGA2 and protein leucine methylation drive pancreatic cancer lineage plasticity
Dobersch, S., Yamamoto, N., Schutter, A., Cavender, S. M., Robertson, T. M., Kartha, N., Samraj, A. N., Doron, B., Poole, L. A., Wladyka, C. L., et al. (2025) · Nature Communications · doi:10.1038/s41467-025-60129-1 · Cited by 8
ETVs dictate hPSC differentiation by tuning biophysical properties
Ziojła, N. M., Socha, M., Guerra, M. C., Kizewska, D. K., Blaszczyk, K., Urbaniak, E., Henry, S., Grabowska, M., Niakan, K. K., Warmflash, A., et al. (2025) · Nature Communications · doi:10.1038/s41467-025-56591-6 · Cited by 6
Ding, L., Roeck, K., Zhang, C., Zidek, B., Rodman, E., Hernandez-Barco, Y. G., Zhang, J.-S., Bamlet, W., Oberg, A., Zhang, L.-Z., et al. (2022) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2022.853003 · Cited by 6
“5, making Ptf1a/p48 another commonly used promoter for Cre-driver lines in pancreas research (Kawaguchi et al., 2002; Magnuson and Osipovich, 2013).”
BackgroundL’îlot pancréatique : ce que nous savons 150 ans après Langerhans
Mandarim-de-Lacerda, C. A. (2019) · Bulletin de l'Académie Nationale de Médecine · doi:10.1016/j.banm.2019.06.015 · Cited by 6
Giannios, I., Serafimidis, I., Anastasiou, V., Pezzolla, D., Lesche, M., Andree, C., Bickle, M., & Gavalas, A. (2019) · Stem Cells · doi:10.1002/stem.2979 · Cited by 6
Obana, E. A., Zhou, Q., Furmanski, O., & Doughty, M. L. (2018) · Journal of Neuroscience Research · doi:10.1002/jnr.24247 · Cited by 6
“The Ptf1a mouse line (Kawaguchi et al., 2002) was obtained from the Mutant Mouse Resource and Research Center at the University of North Carolina in Chapel Hill.”
BackgroundMethodInfluentialDevelopmental Molecular Biology of the Pancreas
Murtaugh, L. C., Cleaver, O. B., & MacDonald, R. J. (2018) · Springer eBooks · doi:10.1007/978-1-4939-7193-0_4 · Cited by 23
Self-citationGeneration of Insulin-Expressing Cells in Mouse Small Intestine by Pdx1, MafA, and BETA2/NeuroD
Lee, S.-H., Rhee, M., Kim, J.-W., & Yoon, K.-H. (2017) · Diabetes & Metabolism Journal · doi:10.4093/dmj.2017.41.5.405 · Cited by 6
“Both pancreatic progenitor cells and gut progenitor cells are derived from the endodermal epithelium and proceed through related developmental pathways [18,19].”
BackgroundMiyatsuka, T. (2015) · Diabetology International · doi:10.1007/s13340-015-0233-z · Cited by 5
“[31], and found that the persistent upregulation of Pdx1 induces acinar-to-ductal metaplasia in a cell-autonomous manner [32].”
BackgroundCampos, M., Lobo, V. J. S.-A., Rodolosse, A., Gottardi, C., Mafficini, A., Beghelli, S., Scardoni, M., Bassi, C., Scarpa, A., & Real, F. (2013) · Biochemical Journal · doi:10.1042/bj20120873 · Cited by 6
Sarkar, S., Lee, C. E., Tipney, H., Karimpour-Fard, A., Dinella, J. D., Juhl, K., Walters, J. A., Hutton, J., & Hunter, L. (2012) · Pancreas · doi:10.1097/mpa.0b013e31823d0160 · Cited by 6
Dateki, M., Kunitomo, M., Yoshioka, K., Yanai, K., Nakasono, S., & Negishi, T. (2011) · Journal of Receptor and Signal Transduction Research · doi:10.3109/10799893.2010.538405 · Cited by 6
Exploring a behavioral role for presynaptic inhibition at spinal sensory-motor synapses
Fink, A. J. (2013) · doi:10.7916/d8b85gh9 · Cited by 6
“Ptf1a-Cre mice (Ptf1aCre mice) express Cre-recombinase under the control of the Ptf1a promoter (Kawaguchi et al., 2002), allowing for restricted expression of reporter genes within Ptf1a-derived neurons.”
BackgroundMethodLester, L. B. (2005) · Humana Press eBooks · doi:10.1385/1592599001 · Cited by 5
TBX3 is dynamically expressed in pancreatic organogenesis and fine-tunes regeneration
Melzer, M. K., Schirge, S., Gout, J., Arnold, F., Srinivasan, D., Burtscher, I., Allgöwer, C., Mulaw, M., Zengerling, F., Günes, C., et al. (2023) · BMC Biology · doi:10.1186/s12915-023-01553-x · Cited by 5
“Specific recombination in epithelial cells of the pancreas was confirmed by immunohistochemical stainings for tdRFP in Ptf1aCre/+ [35] x LSL-tdRFPKI/KI [55, 56] mice (Additional file 1: Fig.”
BackgroundMethodInfluentialSingle-cell and spatial transcriptomics in endocrine research
Matsumoto, R., & Yamamoto, T. (2024) · Endocrine Journal · doi:10.1507/endocrj.ej23-0457 · Cited by 7
“Acinar cells differentiate from multipotent progenitor cells under the regulation of transcription factors, such as PTF1A (pancreas tran‐ scription factor 1 subunit alpha) and MIST1 (Bhlha15, basic helix-loop-helix family member A15) [27].”
Key transcriptional effectors of the pancreatic acinar phenotype and oncogenic transformation
Azevedo-Pouly, A., Hale, M. A., Swift, G. H., Hoàng, C., Deering, T. G., Xue, J., Wilkie, T. M., Murtaugh, L., & MacDonald, R. J. (2023) · PLoS ONE · doi:10.1371/journal.pone.0291512 · Cited by 5
Self-citationKRAS Inhibition Activates an Actionable CD24 “Don’t Eat Me” Signal in Pancreatic Cancer
Wei, Y.-K., Liu, M.-H., Yen, E.-Y., Yao, J., Xun, Z.-Z., Nguyen, P. T., Wang, X.-F., Yang, Z.-C., Yousef, A., Pan, D. N., et al. (2023) · bioRxiv · doi:10.1101/2023.09.21.558891 · Cited by 5
Modulation of transcription factors by small molecules in β-cell development and differentiation
Harithpriya, K., Jayasuriya, R., Adhikari, T., Rai, A., & Ramkumar, K. M. (2023) · European Journal of Pharmacology · doi:10.1016/j.ejphar.2023.175606 · Cited by 5
Altman, M. K., Schaub, C. M., Dickerson, M. T., Dadi, P., Graff, S. M., Galletta, T. J., Amarnath, G., Thorson, A. S., Gu, G.-Q., & Jacobson, D. (2020) · bioRxiv · doi:10.1101/2020.07.15.204974 · Cited by 5
“development [11-14], TRPM7 could also serve an important role in the development of the endocrine pancreas.”
BackgroundIllustrated Abdominal Surgery: Based on Embryology and Anatomy of the Digestive System
Shinohara, H. (2020) · doi:10.1007/978-981-15-1796-9 · Cited by 5
“The dorsal pancreas arises from the duodenum [4], grows in the dorsal mesoduodenum, and eventually extends into the dorsal mesogastrium.”
BackgroundArid1a loss potentiates pancreatic β-cell regeneration through activation of EGF signaling
Celen, C., Chuang, J., Shen, S., Otto, J. E., Collings, C. K., Luo, X.-Y., Li, L., Wang, Y., Wang, Z., Jia, Y.-M., et al. (2020) · bioRxiv · doi:10.1101/2020.02.10.942615 · Cited by 5
“To rule out potential paracrine or endocrine effects, we used Ptf1a-Cre; Arid1aFl/Fl mice to induce deletion in non-β-cells in the pancreas.”
InfluentialChapter 43 – Thymus and Parathyroid Organogenesis
O'Neill, K. E., Nowell, C. S., Richie, E., Manley, N., & Blackburn, C. (2013) · Elsevier eBooks · doi:10.1016/b978-0-12-398358-9.00043-4 · Cited by 5
Basics and applications of stem cells in the pancreas
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Microarray analysis of Xenopus endoderm expressing Ptf1a
Bilogan, C., & Horb, M. E. (2012) · Genesis · doi:10.1002/dvg.22048 · Cited by 5
“The basic helix-loop-helix (bHLH) protein Ptf1a (pancreas specific transcription factor 1a) is one of the first endodermal transcription factors restricted to early pancreatic progenitors before overt morphogenesis of the dorsal and ventral buds (Kawaguchi et al., 2002).”
Dimicoli-Salazar, S., Bulle, F., Yacia, A., Massé, J., Fichelson, S., & Vigon, I. (2011) · Biology of the Cell · doi:10.1042/bc20100112 · Cited by 5
“…experiments relating to enforced expression of master transcription factors in pluripotent embryonic cells or in adult somatic cells have demonstrated the possibility of changing their cell fate and thus generating ascertained cell populations (Okada, 1980; Gehring, 1996; Kawaguchi et al., 2002).”
BackgroundExpression and localization of mesothelin in developing rat pancreas
Hou, L.-Q., Wang, Y.-H., Liu, L.-J., Guo, J., Teng, L., Cao, L.-H., Shi, H., Yuan, L., & Wei, D. (2008) · Development, Growth and Differentiation · doi:10.1111/j.1440-169x.2008.01047.x · Cited by 5
“Several genetic tracing experiments have shown that both exocrine and endocrine cells of the pancreas derive from a pool of pancreatic epithelium and that soluble factors produced by mes- enchyme are crucial for proper pancreatic development (Scharfmann 2000; Gu et al. 2002; Kawaguchi et al. 2002).”
BackgroundJensen, J. (2007) · Current Opinion in Endocrinology, Diabetes & Obesity · doi:10.1097/med.0b013e32827035dd · Cited by 5
Caring for Children Born Small for Gestational Age
Fahlbusch, F., Alcazar, M. A. A., Apple, S., Bilbao, N., Dötsch, J., Eggermann, T., Ertan, A. K., Ertan, A., Finken, M. J. J., Harder, T., et al. (2013) · doi:10.1007/978-1-908517-90-6 · Cited by 4
Nuclear Reprogramming and Stem Cells
Ainscough, J., 山中, 伸., & 多田, 高. (2012) · Stem Cell Biology and Regenerative Medicine · doi:10.1007/978-1-61779-225-0 · Cited by 5
Pancreatic cells and their progenitors.
Salpeter, S., & Dor, Y. (2006) · Methods in Enzymology · doi:10.1016/s0076-6879(06)19013-8 · Cited by 5
Chapter 114 – Development of the Exocrine Pancreas
Werlin, S., & Lee, P. (2004) · doi:10.1016/b978-0-7216-9654-6.50117-x · Cited by 5
Barinova, A., Bogomolova, A. Y., Bogomazova, A., Borisova, A. A., Kiselev, S. L., & Panova, A. (2025) · International Journal of Molecular Sciences · doi:10.3390/ijms26178749 · Cited by 4
“Unlike PDX1, PTF1a expression in the endoderm is specific to pancreatic progenitor cells and does not initiate development of other digestive system organs [16].”
Mima, A., Kimura, A., Ito, R., Hatano, Y., Tsujimoto, H., Mae, S.-I., Yamane, J., Fujibuchi, W., Uza, N., Toyoda, T., et al. (2025) · Scientific Reports · doi:10.1038/s41598-025-88690-1 · Cited by 4
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“Moreover, preventing or reversing tumor initiation in mice may be achieved by maintaining or reintroducing pancreas transcription factor 1A (PTF1A), a key regulator of acinar cell differentiation [24,25], in the presence of Kras G12D and in fl ammation [26 – 28].”
BackgroundDendritic Inhibition by Shh Signaling-Dependent Stellate Cell Pool Is Critical for Motor Learning
Li, W., Chen, L., Fleming, J. T., Brignola, E., Zavalin, K., Lagrange, A. H., Rex, T. S., Heiney, S. A., Wojaczynski, G. J., Medina, J. F., et al. (2021) · Journal of Neuroscience · doi:10.1101/2021.04.15.439999 · Cited by 4
“Ptf1a Cre/+ , Cre was inserted into the endogenous Ptf1a locus, creating a null allele and activating Cre expression in a pattern indistinguishable from that of Ptf1a (Kawaguchi et al , 2002).”
BackgroundMethodRegulation of retinal amacrine cell generation by miR-216b and Foxn3
Zhang, H., Zhuang, P., Welchko, R. M., Dai, M.-H., Meng, F., & Turner, D. (2020) · bioRxiv · doi:10.1101/2020.10.28.358069 · Cited by 4
“Ptf1a mutant mice have the Ptf1a coding region replaced with the Cre coding region (Kawaguchi et al., 2002).”
BackgroundUrade, M., & Fujimoto, S. (2019) · Clinical Journal of Gastroenterology · doi:10.1007/s12328-019-01073-8 · Cited by 4
Pancreas-specific miR-216a regulates proliferation and endocrine and exocrine cell function in vivoPreprint
Erener, S., Ellis, C. E., Ramzy, A., Glavas, M. M., O’Dwyer, S. M., Pereira, S., Wang, T., Pang, J., Bruin, J. E., Riedel, M. J., et al. (2019) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/792655 · Cited by 1
Talbot, N., Shannon, A. E., & Garrett, W. (2019) · In vitro Cellular & Developmental Biology-Animal · doi:10.1007/s11626-019-00336-5 · Cited by 4
Epigenetic-Mediated Reprogramming of Pancreatic Endocrine Cells
Mathiyalagan, P., Keating, S. T., Al‐Hasani, K., & El‐Osta, A. (2015) · Antioxidants and Redox Signaling · doi:10.1089/ars.2014.6103 · Cited by 3
“Both a and b -cells are marked by specific expression of endocrine transcription factors such as the Pancreas transcription factor 1 subunit alpha (Ptf1 a ), indicating a common developmental progenitor (30, 46).”
Wharton's Jelly Mesenchymal Stem Cells for the Treatment of Type 1 Diabetes
Anzalone, R., Iacono, M., Corsello, T., Rastellini, C., Cicalese, L., Farina, F., & Larocca, G. (2014) · doi:10.1007/978-1-4939-1118-9_28 · Cited by 4
“transcription factor 1a) [ 17 , 20 , 21 ].”
Ptf1a control of Dll1 reveals an alternative to the lateral inhibition mechanism
Ahnfelt-Rønne, J., Jørgensen, M. C., Klinck, R., Jensen, J., Füchtbauer, E., Deering, T. G., MacDonald, R. J., Wright, C. V., Madsen, O., & Serup, P. (2012) · Development · doi:10.1242/dev.090597 · Cited by 4
“…(Dll1lacZ/+) (Hrabe de Angelis et al., 1997), Tg(Hes1-EGFP)1Hri BAC transgenic (Klinck et al., 2011), Neurog3tTA/+ (Wang et al., 2009), Ptf1aCre/+ (Kawaguchi et al., 2002) and Hes1+/– (Ishibashi et al., 1995) mouse lines were all kept as heterozygotes and genotyped by PCR and Southern blotting as…”
BackgroundMethodInfluentialSelf-citationDelisle, J. C., Martignat, L., Bach, J., Bösch, S., & Louzier, V. (2008) · BMC Research Notes · doi:10.1186/1756-0500-1-136 · Cited by 4
“Ngn3-positive cells derive from progenitors that express Ptf1a and, henceforth, Ngn3 and Ptf1a are usually co-expressed in pancreatic multipotent progenitors [3,23].”
BackgroundTranscription factors as therapeutic targets for diabetes
Miyatsuka, T., Matsuoka, T., & Kaneto, H. (2008) · Expert Opinion on Therapeutic Targets · doi:10.1517/14728222.12.11.1431 · Cited by 16
“Previous studies using lineage tracing demonstrated that cells expressing another pancreatic transcription factor, Ptf1a, give rise to all three types of pancreatic tissue and supports the specification of precursors of all three pancreatic cell types [113] .”
ResultTissue-specific deletion of c-Jun in the pancreas has limited effects on pancreas formation
Yamamoto, K., Miyatsuka, T., Tanaka, A., Toyoda, S., Kato, K., Shiraiwa, T., Fujitani, Y., Yamasaki, Y., Hori, M., Matsuhisa, M., et al. (2007) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2007.09.056 · Cited by 4
Engineering islets: lessons from stem cells and embryonic development.
Doyle, M. J., & Sussel, L. (2004) · Endocrinology and metabolism clinics of North America (Print) · doi:10.1016/s0889-8529(03)00100-2 · Cited by 4
Development and Anatomy of the Bile Duct
Enomoto, K., & Nishikawa, Y. (2017) · Springer eBooks · doi:10.1007/978-981-10-3500-5_1 · Cited by 5
Regulation of Insulin Secretion and Islet Cell Function
Weir, G., Bonner-Weir, S., & Sharma, A. J. (2012) · Springer eBooks · doi:10.1007/978-1-4614-1028-7_1 · Cited by 4
Reprogramming into pancreatic endocrine cells based on developmental cues
Kordowich, S., Mansouri, A., & Collombat, P. (2009) · Molecular and Cellular Endocrinology · doi:10.1016/j.mce.2009.12.016 · Cited by 27
Frequency-dependent cerebellar circuits independently gate social vocalizations and movement
Brandenburg, C., Srivastava, S., Hipolito, A. G. R., Lin, T., Arenkiel, B. R., & Sillitoe, R. (2026) · bioRxiv · doi:10.64898/2026.02.18.706564 · Cited by 3
Beclin1 is essential for the pancreas development
Mehanna, S., Arakawa, S., Imasaka, M., Chen, W., Nakanishi, Y., Nishiura, H., Shimizu, S., & Ohmuraya, M. (2023) · Developmental Biology · doi:10.1016/j.ydbio.2023.09.008 · Cited by 4
Abnormal outer hair cell efferent innervation in Hoxb1-dependent sensorineural hearing loss
Bonito, M. D., Bourien, J., Tizzano, M., Harrus, A.-G., Puel, J., Avallone, B., Nouvian, R., & Studer, M. (2023) · PLoS Genetics · doi:10.1371/journal.pgen.1010933 · Cited by 3
Exploring the immunological role and prognostic potential of PPM1M in pan-cancer
Zeng, R., Wang, L., Zhang, Y., Yang, Y., Yang, J., & Qin, Y. (2023) · Medicine · doi:10.1097/md.0000000000032758 · Cited by 3
“Each tissue was sliced to a thickness of 4 mm,[17] embedded in wax blocks, and finally fixed on glass slides.”
MethodFu, J., Ling, J., Li, C.-F., Tsai, C.-L., Yin, W., Hou, J., Chen, P.-H., Cao, Y., Kang, Y., Sun, Y., et al. (2022) · bioRxiv · doi:10.1038/s41467-024-47242-3 · Cited by 3
Borromeo, M. D., Meredith, D., Castro, D. S., Chang, J. C., Tung, K.-C., Guillemot, F., & Johnson, J. E. (2017) · Development · doi:10.1242/dev.155986 · Cited by 3
“4kbPtf1a::mCherry line was crossed to the Ptf1a knockin mouse (Kawaguchi et al., 2002), and mCherry+ cells were isolated from Ptf1a−/+ and Ptf1a−/− neural tubes.”
MethodBradford, E. M. (2016) · World Journal of Gastrointestinal Pathophysiology · doi:10.4291/wjgp.v7.i1.138 · Cited by 4
“Expression of Pdx1 is a key regulatory step in the development of both the pancreas and the duodenum [20] , and inactivation of Ptf1a drives pancreatic precursor cells toward intestinal cell fates [21] .”
Zhao, Z.-M., Xi, H.-F., Xu, D.-B., & Li, C.-G. (2015) · Tumor Biology · doi:10.1007/s13277-015-3466-3 · Cited by 3
“K-ras (G12D) mice [16, 17] and Ptf1a promoter Cre reporter (Ptf1a-Cre) mice [7, 18] were both purchased from the Jackson Labs (Bar Harbor, ME, USA).”
MethodRetractedReprogramming into pancreatic endocrine cells based on developmental cues
Kordowich, S., Mansouri, A., & Collombat, P. (2009) · Molecular and Cellular Endocrinology · doi:10.1016/j.mce.2009.10.015 · Cited by 37
Pancreas Biology, Pathology, and Tissue Engineering
Macfarlane, W. M., Bone, A. J., & Harrison, M. (2008) · Springer eBooks · doi:10.1007/978-0-387-74660-9_8 · Cited by 1
Pancreatic Adenocarcinoma: How
Bhattacharya, U. (2015) · doi:10.6004/jnccn.2007.0085 · Cited by 3
TGF-β as Tumor Suppressor: Lessons from Mouse Models
Valcourt, U., Vincent, D., & Bartholin, L. (2013) · Springer eBooks · doi:10.1007/978-4-431-54409-8_6 · Cited by 3
Lineage Tracing of Pancreatic Stem Cells and Beta Cell Regeneration
Houbracken, I., Mathijs, I., & Bouwens, L. (2012) · Methods in molecular biology · doi:10.1007/978-1-62703-068-7_20 · Cited by 3
37 – Thymus and Parathyroid Organogenesis
Manley, N., & Blackburn, C. (2004) · Elsevier eBooks · doi:10.1016/b978-012436643-5/50046-8 · Cited by 3
Molecular dynamics driving phenotypic divergence among KRAS mutants in pancreatic tumorigenesis
Grimont, A., Falvo, D. J., Sisso, W. J., dos Santos, F., Chan, C. W., Zumbo, P., Fall, W. B., Ferrick, K. R., Pan, G., Cleveland, M., et al. (2026) · Developmental Cell · doi:10.1016/j.devcel.2026.06.016 · Cited by 4
ATM Deficiency Induces TGFβ-Mediated Stromal Programming in Pancreatic Cancer
Roger, É., Mummey, H. M., Zimmer, E., Srinivasan, D., Härle, A., Moubri, L., Michels, A. K., Singh, R., Ekizce, M., Melzer, M. K., et al. (2026) · Cancer Research · doi:10.1158/0008-5472.can-26-0138 · Cited by 4
Unger, L., Larsen, U., Legøy, T. A., Hossain, M. K., Gudmestad, J. H., Friestad, A., Sharmine, S., Njølstad, P., Ræder, H., Herrera, P., et al. (2026) · Genes & Development · doi:10.1101/gad.353153.125 · Cited by 2
“Ptf1a is a master regulator of pancreas development, directing progenitors toward a pancreas instead of an intestinal cell fate (Kawaguchi et al. 2002), suggesting that the observed intestinal elongation in the Pdx1-Hnf1a model is driven by the mutation within the intestinal tissue itself,…”
Srinivasan, D., Roger, E., Perkhofer, L., Zimmer, E., Barth, T. F., Mosler, J. P., Härle, A., Weissinger, S., Gaisa, N., Möller, P., et al. (2025) · Advancement of science · doi:10.1002/advs.202417606 · Cited by 2
Misfolding CPA1 mutation accelerates precancerous pancreas lesions in KC mice
Demcsák, A., & Sahin-Tóth, M. (2025) · American Journal of Physiology - Gastrointestinal and Liver Physiology · doi:10.1152/ajpgi.00025.2025 · Cited by 2
Suzuki, Y., Sugimori, M., Kanemaru, Y., Onodera, S., Tsuchiya, H., Ikeda, A., Ikeda, R., Goda, Y., Kaneko, H., Irie, K., et al. (2025) · PLoS ONE · doi:10.1371/journal.pone.0326491 · Cited by 2
“1(cre)Cvw (Ptf1a Cre/+ ) mice was generous gift from Prof. Christopher V. Wright [16].”
Reprogramming of Different Cell Lineages into Functional β-Cell Substitutes
Dattoli, A. A., Kelemen, Y., & Huang, X. (2025) · Cellular Reprogramming · doi:10.1089/cell.2024.0102 · Cited by 3
“More studies in this direction involve the overexpression of other important TFs, including PTF1A, which was shown to convert stomach and intestinal tissue into both pancreatic endocrine and acinar cells (Kawaguchi et al., 2002).”
Degradation meets development: Implications in β‐cell development and diabetes
Ashok, A., Kalthur, G., & Kumar, A. (2024) · Cell Biology International · doi:10.1002/cbin.12155 · Cited by 2
“PTF1A (Pancreas TF 1a) is one of the TF required for early pancreatic development (Kawaguchi et al., 2002; Krapp et al., 1998) and especially enables the maintenance of acinar cell homeostasis (Dong et al., 2008; Masui et al., 2010).”
BackgroundTsujimoto, A., Matsuo, N., Lai, X., Inoue, T., Yoda, H., Lin, J., Shinozaki, Y., Watanabe, T., Koshikawa, N., Takatori, A., et al. (2022) · Cancer Medicine · doi:10.1002/cam4.5359 · Cited by 2
Fujiyama, T., Takenaka, H., Asano, F., Miyanishi, K., Hotta-Hirashima, N., Ishikawa, Y., Kanno, S., Seoane-Collazo, P., Miwa, H., Hoshino, M., et al. (2022) · Frontiers in Behavioral Neuroscience · doi:10.3389/fnbeh.2022.910461 · Cited by 2
“Since Ptf1a is required for the development of the pancreas (Kawaguchi et al., 2002), we performed GTT.”
BackgroundMethodGirnyi, S., Ekman, M., Marano, L., Roviello, F., & Polom, K. (2021) · Current Oncology · doi:10.3390/curroncol28060413 · Cited by 2
“This process is controlled by the pdx1 and ptf1a genes [21,49].”
BackgroundCobo, I., Paliwal, S., Melià-Alomà, J., Torres, A., Martínez-Villarreal, J., García, F., Millán, I., Pozo, N. D., Park, J.-C., MacDonald, R. J., et al. (2021) · bioRxiv · doi:10.1101/2021.08.09.455477 · Cited by 2
Self-citationKuwabara-Ohmura, Y., Iizuka, K., Liu, Y.-Y., Takao, K., Nonomura, K., Kato, T., Mizuno, M., Hosomichi, K., Tajima, A., Miyazaki, T., et al. (2020) · Endocrine journal · doi:10.1507/endocrj.ej20-0038 · Cited by 2
“Among them, PTF1A deficiency results in a hypoplastic dorsal bud and a total lack of acinar cells [15, 16].”
BackgroundA pancreas specific Ptf1a-driven Cre mouse line causes paternally transmitted germline recombination
Kabacaoglu, D., Lesina, M., & Algül, H. (2020) · bioRxiv · doi:10.1101/2020.03.13.989178 · Cited by 2
“Several studies showed PTF1A expression in developing pancreas [16], neural tube [20], and cerebellum [21,22].”
Background
Metadata
- Authors
- Kawaguchi, Y., Cooper, B., Gannon, M., Ray, M., MacDonald, R. J., & Wright, C. V. E.
- Affiliations
- Vanderbilt University (US)
- The University of Texas Southwestern Medical Center (US)
- Corresponding author
- Wright, Christopher V.E.
- Venue
- Nature Genetics
- Published
- 2002-08-19
- Volume
- 32
- Issue
- 1
- Pages
- 128-134
- ISSN
- 1061-4036 (ISSN-L)
- 1546-1718
- OpenAlex
- W1993055783
- Cited by
- 1,007
- References
- 26
- Citations by year
- 2026: 18 · 2025: 30 · 2024: 18 · 2023: 39 · 2022: 23 · 2021: 39 · 2020: 39 · 2019: 44 · 2018: 43 · 2017: 44 · 2016: 44 · 2015: 62 · 2014: 54 · 2013: 65 · 2012: 68
- FWCI
- 35.56
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature Genetics (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Pancreatic function and diabetes
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Developmental Biology and Gene Regulation
- Health Sciences › Medicine › Oncology › Pancreatic and Hepatic Oncology Research
- Keywords
- Ptf1a, pancreatic development, foregut endoderm, pancreatic progenitors, duodenal epithelium, pancreatic stem cells, PDX1, cis-regulatory sequences, lineage tracing, organogenesis
- MeSH terms
- Animals, Cell Differentiation, Duodenum, Gene Expression Regulation, Pancreas, Transcription Factors, Trans-Activators, Homeodomain Proteins, Cell Lineage, Animals, Genetically Modified, Mice
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