Expression and functional studies of the GDNF family receptor alpha 3 in the pancreas.

ABSTRACT: The generation of therapeutic ?-cells from human pluripotent stem cells relies on the identification of growth factors that faithfully mimic pancreatic ?-cell development in vitro. In this context, the aim of the study was to determine the expression and function of the glial cell line derived neurotrophic factor receptor alpha 3 (GFR?3) and its ligand artemin (Artn) in islet cell development and function. GFR?3 and Artn expression were characterized by in situ hybridization, immunochemistry, and qRT-PCR. We used GFR?3-deficient mice to study GFR?3 function and generated transgenic mice overexpressing Artn in the embryonic pancreas to study Artn function. We found that GFR?3 is expressed at the surface of a subset of Ngn3-positive endocrine progenitors as well as of embryonic ?- and ?-cells, while Artn is found in the pancreatic mesenchyme. Adult ?-cells lack GFR?3 but ?-cells express the receptor. GFR?3 was also found in parasympathetic and sympathetic intra-islet neurons as well as in glial cells in the embryonic and adult pancreas. The loss of GFR?3 or overexpression of Artn has no impact on Ngn3 and islet cell formation and maintenance in the embryo. Islet organization and innervation as well as glucose homeostasis is normal in GFR?3-deficient mice suggesting functional redundancy.

SUBMITTER: Nivlet L 

PROVIDER: S-EPMC5911917 | biostudies-literature | 2016 Feb

REPOSITORIES: biostudies-literature