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

Abstract

The generation of therapeutic β-cells from human pluripotent stem cells relies on the identification of growth factors that faithfully mimic pancreatic β-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 α 3 (GFRα3) and its ligand Artemin in islet cell development and function. GFRα3 and Artn expression were characterized by in situ hybridization, immunochemistry and qRT-PCR. We used GFRα3-deficient mice to study GFRα3 function and generated a transgenic mice overexpressing Artn in the embryonic pancreas to study Artn function. We found that GFRα3 is expressed at the surface of a subset of Ngn3-positive endocrine progenitors as well as of embryonic α- and β-cells, while Artn is found in the pancreatic mesenchyme. Adult β-cells lack GFRα3 but α-cells express the receptor. GFRα3 was also found in parasympathetic and sympathetic intra islets neurons as well as in glial cells in the embryonic and adult pancreas. The loss of GFRα3 or overexpression of Artn has no impact on Ngn3- and islet- cells formation and maintenance in the embryo. Islet organisation and innervation as well as glucose homeostasis is normal in GFRα3-deficient mice suggesting functional redundancy.

Neurog3-dependent pancreas dysgenesis causes ectopic pancreas in Hes1 mutant mice

“…However, as shown in Fig. S5, Gfra3 was largely confined to endocrine cells as previously noted (Nivlet et al, 2016), and no difference between Hes1 −/− and controls was observed. Podocalyxin-like was found at the apical side of most epithelial cells, wherever a microlumen had formed, but again without a noticeable difference between Hes1 −/− and controls.…”