Expression and functional studies of the GDNF family receptor alpha 3 in the pancreas.
J Mol Endocrinol
; 56(2): 77-90, 2016 Feb.
Article
in En
| MEDLINE
| ID: mdl-26576643
ABSTRACT
The generation of therapeutic ß-cells from human pluripotent stem cells relies on the identification of growth factors that faithfully mimic pancreatic ß-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 (GFRα3) and its ligand artemin (Artn) 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 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 ß-cells, while Artn is found in the pancreatic mesenchyme. Adult ß-cells lack GFRα3 but α-cells express the receptor. GFRα3 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 GFRα3 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 GFRα3-deficient mice suggesting functional redundancy.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Islets of Langerhans
/
Glial Cell Line-Derived Neurotrophic Factor Receptors
Type of study:
Prognostic_studies
Limits:
Animals
Language:
En
Journal:
J Mol Endocrinol
Journal subject:
BIOLOGIA MOLECULAR
/
ENDOCRINOLOGIA
Year:
2016
Document type:
Article
Affiliation country:
France