Study of G alpha s requirement for pancreatic islet cell development

RODRÍGUEZ SEGUÍ, S.A.; STEFFEN, DANA; TRABA, S.A.; ROMERO, AGUSTÍN; PINKASZ, MARINA; MONTENEGRO, MAURICIO; GUTKIND, J. SILVIO

Bariloche

Simposio; Fourth South American Symposium in Signal Transduction and Molecular Medicine (SISTAM); 2018

International Union of Biochemistry and Molecular Biology (IUBMB).

We have previously reported the construction ofgenomic cisregulatory maps in human embryonic pancreas of 6-7 wpc and invitro pancreatic progenitor cellsderived from human pluripotent stem cells. Analysis of theseepigenomic maps led to the discovery that TEAD and YAP are importantgene expression regulators in the embryonic pancreas. In more detail,we found that the nuclear localization of the coactivator YAP isimportant for maintaining the phenotype of pancreatic multipotentprogenitor cells, while downregulation of this factor is seen inendocrine commited cells. To date, it is not clear which upstreamsignaling cues, acting during normal pancreas development, cause thedownregulation of YAP and its regulated gene network that mightultimately allow endocrine commitment. Our preliminary resultssuggest that a subset of the genes preferentially active inpancreatic progenitor cells could be inhibited by the Gprotein-coupled receptor (GPCR) signaling network. Thissignaling network could be interacting with the mechanisms controledby TEAD and YAP during βcell development, similarly to whatwas recently reported in folicullar epithelial cells. Here,we used transgenic mice to allow for theconditional deletion of the Gnasgene (coding for the Gαs protein) in the pancreas. Our preliminaryresults suggest that these mice present ametabolic defect (associated with lower weight) due to an alterationin pancreatic islet cell composition. p { margin-bottom: 0.1in; direction: ltr; line-height: 115%; text-align: left; }a:link { color: rgb(0, 0, 255); }