Control of pancreas formation and regeneration

Sonja Töchterle, Dominik Regele, Marc Sathianathan, Nargess Shahbazi, Rosalite Dittrich, Robin Kimmel, Dirk Meyer

The pancreas is a vertebrate specific organ with essential functions in glucose regulation and food digestion. It consists of endocrine cell clusters, the islets, exocrine tissue surrounding the islets, and a duct system connecting exocrine and gut system. An important function of the endocrine cells is the production of insulin. Fish and mammals show a very similar pancreas architecture and use a highly conserved set of genes to control pancreas formation. Therefore the zebrafish is an ideal system for diabetes-related research.

We study the molecular control of endocrine differentiation and organ morphogenesis. A major focus is laid on the characterization fo the Hlxb9-related transcription factors Mnx1, Mnx2a and Mnx2b. These factors have conserved functions in pancreas formation and differentiation of insulin-producing β-cells. In addition, they are required for motoneuron differentiation and heterozygous loss of human Mnx1 is the major cause of sacral agenesis in patients suffering Currarino syndrome.

Research_Pancreas_01

Selected Publications

Temocin, O.; Regele, D.; Sathianathan, M.; Überbacher, C.; Hartl, M.; Edenhofer, F.; Meyer, D. (2021): Generation of an hiPSC-1 knock-in line expressing TY1-tagged MNX1-protein together with mScarlet. In Stem cell Research 56, Nr. 102522 Epub 2021 Sep2 Doi: 10.1016/j.scr.2021.102522. Pubmed

Emfinger CH, Lőrincz R, Wang Y, York NW, Singareddy SS, Ikle JM, Tryon RC, McClenaghan C, Shyr ZA, Huang Y, Reissaus CA, Meyer D, Piston DW, Hyrc K, Remedi MS, Nichols CG. Beta-cell excitability and excitability-driven diabetes in adult Zebrafish islets. Physiological Reports 2019 Jun;7(11):e14101. DOI: 10.14814/phy2.14101. Pubmed

Lorincz R, Emfinger CH, Walcher A, Giolai M, Krautgasser C, Remedi MS, Nichols CG, Meyer D. In vivo monitoring of intracellular Ca²⁺ dynamics in the pancreatic β-cells of zebrafish Embryos.In Islets 2018;10(6):221-238. (DOI) 2018.1540234. Epub 2018 Dec 6. Pubmed

Freudenblum J, Iglesias JA, Hermann M, Walsen T, Wilfinger A, Meyer D, Kimmel RA. In vivo imaging of emerging endocrine cells reveals a requirement for PI3K-regulated motility in pancreatic islet morphogenesis. In Development 2018 Feb 8:145(3). (DOI) Pubmed

Facchinello, N; Tarifeño-Saldivia, E; Grisan, E; Schiavone, M; Peron, M; Mongera, A; Ek, O; Schmitner, N; Meyer, D; Peers, B; Tiso, N; Argenton, F; (2017) Tcf7l2 plays pleiotropic roles in the control of glucose homeostasis, pancreas morphology, vascularization and Regeneration. In Scientific Reports 2017; 7: 9605. Published online 2017 Aug 29. (DOI) Pubmed

Li, J; Casteels, T; Frogne,T; Ingvorsen, C; Honoré, C; Courtney, M; Huber, KV; Schmitner, N; Kimmel, RA; Romanov, RA; Sturtzel, C; Lardeau, CH7; Klughammer, J; Farlik, M; Sdelci, S; Vieira, A; Avolio, F; Briand, F; Baburin, I; Májek, P; Pauler, FM; Penz, T; Stukalov, A; Gridling, M; Parapatics, K; Barbieux, C; Berishvili, E; Spittler, A; Colinge, J: Bennett, KL; Hering, S; Sulpice, T; Bock, C; Distel, M; Harkany, T; Meyer, D; Superti-Furga, G; Collombat, P; Hecksher-Sørensen, J; Kubicek S (2017) Artemisinins Target GABAA Receptor Signaling and Impair α cell Identity. In cell 2017 Jan 12;168(1-2):86-100.e15. Epub 2016 Dec 1. (DOI) Pubmed

Kimmel, R.A.; Meyer, D. (2016) Zebrafish Pancreas as a Model for Development and Disease. Methods in cell Biology, available online 17 March 2016. doi:10.1016/bs.mcb.2016.02.009 . Pubmed

Kimmel, R.A., Dobler, S., Schmitner, N., Walsen, T., Freudenblum, J., and Meyer, D. (2015). Diabetic pdx1-mutant zebrafish show conserved responses to nutrient overload and anti-glycemic treatment. Sci. Rep. 5, 14241 Pubmed

Liu, M., Schmitner, N., Sandrian, M.G., Zabihian, B., Hermann, B., Salvenmoser, W., Meyer, D., Drexler, W., (2013) In vivo three dimensional dual wavelength photoacoustic tomography imaging of the far red fluorescent protein E2-Crimson expressed in adult zebrafish, Biomedical Optics Express, Vol. 4, Issue 10, pp. 1846-1855. doi: 10.1364/BOE.4.001846. OpticsInfoBase

Wurzinger G., Nuster R., Schmitner N., Gratt S., Meyer D., Paltauf G. (2013) Simultaneous three-dimensional photoacoustic and laser-ultrasound tomography. Biomed Opt Express. 2013 Jul 19;4(8):1380-9. doi: 10.1364/BOE.4.001380. Pubmed

Nuster R, Schmitner N, Wurzinger G, Gratt S, Salvenmoser W, Meyer D, Paltauf G. (2013) Hybrid photoacoustic and ultrasound section imaging with optical ultrasound detection. J Biophotonics. 2013 May 5. DOI: 10.1002/jbio.201200223. [Epub ahead of print]. PMID: 23650129 PubMed

Wilfinger, A., Arkhipova, V., Meyer D., cell type and tissue specific function of islet genes in zebrafish pancreas development.Dev. Biol. (2013) Volume 378, Issue 1, 1 June 2013, Pages 25–37. doi: 10.1016/j.ydbio.2013.03.009. Science direct

Arkhipova V., Wendik B., Devos N., Ek O., Peers B., Meyer D. (2012) Characterization and regulation of the hb9/mnx1 beta-cell progenitor specific enhancer in zebrafish. Dev Biol. 2012 May 1;365(1):290-302. Epub 2012 Mar 9. DOI: 101016, Pubmed

Nuster R., Gratt S., Passler K., Meyer D., and Paltauf G., "Photoacoustic section imaging using an elliptical acoustic mirror and optical detection", J. Biomed. Opt. 17, 030503 (2012), DOI:10.1117/1.JBO.17.3.030503. SPIE Digital Library

Kimmel RA, Onder L, Wilfinger A, Ellertsdottir E, Meyer D. (2011) Requirement for Pdx1 in specification of latent endocrine progenitors in zebrafish. BMC Biol. 2011 Oct 31;9:75. Pubmed

Untergasser, G., Martowicz, A., Hermann, M., Töchterle, S., Meyer, D. (2011) Distinct expression patterns of dickkopf genes during late embryonic development of Danio rerio. Gene Expr Patterns. 2011 Aug 26. Pubmed

Kimmel, R., Meyer, D. (2010) Molecular regulation of pancreas development in zebrafish. Methods cell Biol 100, 261-80 PubMed

Wendik, B., Maier, E., Meyer, D. (2004) Zebrafish mnx genes in endocrine and exocrine pancreas formation Dev. Biol. 268, 372-83 PubMed

Zecchin, E. Mavropoulos, A., Devos, N.,. Filippi, A., Tiso, N., Meyer, D., Peers, B., Bortolussi, M., Argenton, F. (2004) Evolutionary conserved role of ptf1a in the exocrine pancreatic fate. Dev. Biol. 268, 174-84. PubMed

Gnugge, L., Meyer, D. and Driever, W. (2004) Pancreas development in zebrafish. Methods cell Biol 76, 531. PubMed