Islet formation during the neonatal development in mice.
The islet of Langerhans is a unique micro-organ within the exocrine pancreas, which is composed of insulin-secreting beta-cells, glucagon-secreting alpha-cells, somatostatin-secreting delta-cells, pancreatic polypeptide-secreting PP cells and ghrelin-secreting epsilon-cells. Islets also contain non-endocrine cell types such as endothelial cells. However, the mechanism(s) of islet formation is poorly understood due to technical difficulties in capturing this dynamic event in situ. We have developed a method to monitor beta-cell proliferation and islet formation in the intact pancreas using transgenic mice in which the beta-cells are specifically tagged with a fluorescent protein. Endocrine cells proliferate contiguously, forming branched cord-like structures in both embryos and neonates. Our study has revealed long stretches of interconnected islets located along large blood vessels in the neonatal pancreas. Alpha-cells span the elongated islet-like structures, which we hypothesize represent sites of fission and facilitate the eventual formation of discrete islets. We propose that islet formation occurs by a process of fission following contiguous endocrine cell proliferation, rather than by local aggregation or fusion of isolated beta-cells and islets. Mathematical modeling of the fission process in the neonatal islet formation is also presented.
Miller
Kevin
K
Department of Medicine, The University of Chicago, Chicago, IL, USA.
Kim
Abraham
A
Kilimnik
German
G
Jo
Junghyo
J
Moka
Uchenna
U
Periwal
Vipul
V
Hara
Manami
M
D000818:Animals; D019295:Computational Biology / Q000379:methods; D015509:Developmental Biology; D018507:Gene Expression Regulation, Developmental; D007091:Image Processing, Computer-Assisted; D007150:Immunohistochemistry / Q000379:methods; D050417:Insulin-Secreting Cells / Q000166:cytology*; D007515:Islets of Langerhans / Q000166:cytology / Q000196:embryology*; D051379:Mice; D008822:Mice, Transgenic; D008954:Models, Biological; D008962:Models, Theoretical