Serup Group: Developmental Biology of The Pancreas
Our aim is to understand the developmental biology of the pancreas. We wish to understand the signalling events that regulate growth and differentiation of pancreatic cell types with special emphasis on the insulin producing beta cell.
We are particularly interested in understanding how Notch signalling regulates several distinct processes during pancreatic development. The majority of our studies are done with chicken, mice and embryonic stem cells. We use a wide variety of techniques including gene targeting, transgenic mice, gene arrays, immunohistochemistry, confocal microscopy, tissue explants, and in ovo electroporation. The aim of all our experiments is to understand the genetic and cellular interactions that direct pancreatic organogenesis.
We are currently mapping the temporal requirement of Notch signalling in different processes occurring during pancreatic development as well as determining the cell biological details of Notch signalling events. We are also involved in a collaborative tool-generating project that aims to develop new fluorescent reporters for a number of developmental signalling pathways. These tools will significantly improve our ability to study signalling events in vivo and in vitro.
Jorgensen, M.C., de Lichtenberg, K.H., Collin, C.A., Klinck, R., Ekberg, J.H., Engelstoft, M.S., Lickert, H., and Serup, P. (2018). Neurog3-dependent pancreas dysgenesis causes ectopic pancreas in Hes1 mutant mice. Development 145, doi:10.1242/dev.163568.
Seymour, P.A., Collin, C.A., Jorgensen, M.C., Imayoshi, I., Kageyama, R., and Serup, P. (2018). Dll1 and Jag1 are differentially required to specify proximal and distal pancreatic duct compartments. bioRxiv 336529, doi: 10.1101/336529
de Lichtenberg, K.H., Funa, N.S., Nakic, N., Ferrer, J., Zhu, Z., Huangfu, D., and Serup, P. (2018). Genome- wide identification of HES1 target genes uncover novel roles for HES1 in pancreatic development. bioRxiv 335869, doi: 10.1101/335869
Horn, S., Kobberup, S., Jorgensen, M.C., Kalisz, M., Klein, T., Kageyama, R., Gegg, M., Lickert, H., Lindner, J., Magnuson, M.A., Kong, Y.Y., Serup, P., Ahnfelt-Ronne, J., and Jensen, J.N. (2012). Mind bomb 1 is required for pancreatic beta-cell formation. Proceedings of the National Academy of Sciences USA 109, 7356-7361, doi:10.1073/pnas.1203605109.
Ahnfelt-Rønne, J., Jørgensen, M.C., Klinck, R., Jensen, J.N., Füchtbauer, E., Deering, T., MacDonald, R.J., Wright, C.V.E., Madsen, O.D., and Serup, P. (2012). Ptf1a-mediated control of Dll1 reveals an alternative to the lateral inhibition mechanism. Development 139, 39-45, doi: 10.1242/dev.071761.
Kalisz, M., Winzi, M., Bisgaard, H.C., and Serup, P., (2012). EVEN-SKIPPED HOMEOBOX 1 controls human ES cell differentiation by directly repressing GOOSECOID expression. Developmental Biology, 362(1), 94-103, doi:10.1016/j.ydbio.2011.11.017.
Serup, P., Gustavsen, C., Klein, T., Potter, L.A., Lin, R., Mullapudi, N., Wandzioch, E., Hines, A., Davis, A., Bruun, C., Engberg, N., Petersen, D.R., Peterslund, J.M., Macdonald, R.J., Grapin-Botton, A., Magnuson, M.A. and Zaret, K.S. (2012). Partial promoter substitutions generating transcriptional sentinels of diverse signaling pathways in embryonic stem cells and mice. Disease Models and Mechanisms 5, 956-966, doi:10.1242/dmm.009696.
Petersen, D.R., Gustavsen, C., Lindskog, S.R., Magnuson, M.A., Zaret, K.S., and Serup, P. (2012). Engineering Artificial Signalling Centres to Polarize Embryoid Body Differentiation. Stem Cells and Development 21, 647-653, doi: 10.1089/scd.2011.0344
Intestines and Pancreas
Intestines and the pancreas in a 15 day old mouse embryo. The white tissue is the stomach and the duodenum. The red tissue is the part of the pancreas that produces pancreatic digestive enzymes and the green spots are clusters of beta cells.