Cell lineage analysis of pancreatic islet development: glucagon and insulin cells arise from catecholaminergic precursors present in the pancreatic duct.

We have previously reported that cells transiently expressing tyrosine hydroxylase (TH), the first enzyme of the catecholamine biosynthetic pathway, are present in the pancreas of mouse embryos from prenatal Day 11 (E11) and that, at E12, some TH cells contain glucagon. Cells containing TH were also found in adults which, unlike the TH cells of embryos, did not contain glucagon (G. Teitelman, T. H. Joh, and D. J. Reis (1981). Proc. Natl. Acad. Sci. 78, 5225). These findings suggested to us that the TH cells of embryonic pancreas were the precursors of glucagon cells of adults. In this study we used immunocytochemical and autoradiographic techniques to determine whether cells containing TH (a) were present in pancreas throughout pre- and postnatal development, (b) were localized to a specific region of the gland, (c) contained insulin at any time, and (d) proliferated. We found that TH cells were present in pancreas throughout life. In embryos, cells containing TH localized only along the pancreatic duct, also contained either glucagon or insulin, and were able to proliferate. In contrast, after birth, the pancreatic duct contained no TH cells. Cells containing TH in postnatal and adult mice also differed from embryonic TH cells in that they were found in all islets, contained insulin but not glucagon, and did not synthesize DNA, and hence did not proliferate. These findings suggest that progenitor cells that contain catecholamines and are present in the pancreatic duct give rise to glucagon and insulin cells of adult islets. They also indicate that the TH-insulin cells of postnatal and adult mice are not stem cells but are postmitotic cells that appear in the islets after birth.