Expression of the receptor tyrosine kinase KIT in mature beta-cells and inthe pancreas in development

In the pancreas, ligands of receptor tyrosine kinases (RTKs) are thought to be implicated in the development and function of the islets of Langerhans, which represent the endocrine part of the pancreas. In a previous study, w e randomly screened by reverse transcriptase-polymerase chain reaction for RTKs expressed in the embryonic pancreas. One cDNA fragment that was cloned during this screen corresponded to the KIT receptor. The objective of the present study was to analyze the pattern of Kit expression in the pancreas. We demonstrated that Kit is expressed and functional in terms of signal tr ansduction in the insulin-producing cell line INS-1. Indeed, upon treatment with the KIT ligand (KITL), the extracellular signal-regulated protein kin ase was phosphorylated, and the expression of early responsive genes was in duced. We also demonstrated that Kit mRNAs are present in fetal and adult r at islets. We next used mice that had integrated the lac Z reporter gene in to the Kit locus. In these mice, beta -galactosidase (beta -gal) served as a convenient marker for expression of the endogenous Kit gene. Kit was foun d to be specifically transcribed in beta -cells (insulin-expressing cells), whereas no expression was found in other endocrine cell types or in the ex ocrine tissue. Interestingly, not all mature beta -cells expressed Kit, ind icating that Kit is a marker of a subpopulation of beta -cells. Finally, by following beta -gal expression in the pancreas during fetal life, we found that at E 14.5, Kit is expressed in both insulin- and glucagon-expressing cells present at that stage, and also in a specific cell population present in the epithelium that stained negative for endocrine markers. These data suggest that these Kit-positive/endocrine-negative cells could represent a subpopulation of endocrine cell precursors.