Abstract
The transcription factor Pax6 is an important regulator of development and cell differentiation in various organs. Thus, Pax6 was shown to promote neural development in the cerebral cortex and spinal cord, and to control pancreatic endocrine cell genesis. However, the role of Pax6 in distinct endocrine cells of the adult pancreas has not been addressed. We report the conditional inactivation of Pax6 in insulin and glucagon producing cells of the adult mouse pancreas. In the absence of Pax6, beta- and alpha-cells lose their molecular maturation characteristics. Our findings provide strong evidence that Pax6 is responsible for the maturation of beta-, and alpha-cells, but not of delta-, and PP-cells. Moreover, lineage-tracing experiments demonstrate that Pax6-deficient beta- and alpha-cells are shunted towards ghrelin marked cells, sustaining the idea that ghrelin may represent a marker for endocrine cell maturation.
Highlights
The pancreas develops from the endoderm at the foregut/midgut junction to give rise to two main cell compartments, comprising exocrine and endocrine cells
Pancreatic endocrine cell function was shown to depend on Pax6 gene activity
In the present report we studied the consequences of Pax6 conditional inactivation in distinct endocrine cells in the adult mouse pancreas
Summary
The pancreas develops from the endoderm at the foregut/midgut junction to give rise to two main cell compartments, comprising exocrine and endocrine cells. The major compartment of the pancreas is the exocrine tissue (acinar and duct cells) producing digestive enzymes that reach the duodenum through an intricate ductal system. The endocrine counterpart regroups hormone-producing cells into functional units called islets of Langerhans, consisting of beta-, alpha-, delta-, PP-, and epsilon-cells secreting insulin, glucagon, somatostatin, pancreatic polypeptide, and ghrelin, respectively, to control glucose homoeostasis. Pax inactivation resulted in the loss of beta- and delta-cells, concomitant with a proportional increase of glucagon-labeled cells [3]. The forced expression of Pax in glucagon-producing alpha-cells of PLOS ONE | DOI:10.1371/journal.pone.0144597. The forced expression of Pax in glucagon-producing alpha-cells of PLOS ONE | DOI:10.1371/journal.pone.0144597 December 11, 2015
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