TY - JOUR
T1 - GFRα1 expression in cells lacking ret is dispensable for organogenesis and nerve regeneration
AU - Enomoto, Hideki
AU - Hughes, Inna
AU - Golden, Judith
AU - Baloh, Robert H.
AU - Yonemura, Shigenobu
AU - Heuckeroth, Robert O.
AU - Johnson, Eugene M.
AU - Milbrandt, Jeffrey
N1 - Funding Information:
We thank Sanjay Jain and Shigeru Kuratani for helpful discussions. We also thank Kelli Simburger, Amber Neilson, Tatiana Gorodinsky, Nina Panchenko, Hitoshi Miyachi, Mayumi Akatsuka, Naoko Inoue, and Kayoko Inoue for their excellent technical assistance. HB9 antibody and GDNF-deficient mice were kindly provided by Dr. Thomas Jessell and Genentech, respectively. This work was supported by grant AG01373 from the NIA (J.M.), AG13729 (E.M.J.), RIKEN (H.E.), and MEXT “The Project for Realization of Regenerative Medicine” (H.E.). R.O.H. is supported by RO1 DK57038, RO1 DK64592, and a grant from the March of Dimes, FY02-182.
PY - 2004/11/18
Y1 - 2004/11/18
N2 - The GDNF family ligands signal through a receptor complex composed of a ligand binding subunit, GFRα, and a signaling subunit, the RET tyrosine kinase. GFRαs are expressed not only in RET-expressing cells, but also in cells lacking RET. A body of evidence suggests that RET-independent GFRαs are important for (1) modulation of RET signaling in a non-cell-autonomous fashion (trans-signaling) and (2) regulation of NCAM function. To address the physiological significance of these roles, we generated mice specifically lacking RET-independent GFRα1. These mice exhibited no deficits in regions where trans-signaling has been implicated in vitro, including enteric neurons, motor neurons, kidney, and regenerating nerves. Furthermore, no abnormalities were found in the olfactory bulb, which requires proper NCAM function for its formation and is putatively a site of GDNF-GFRα-NCAM signaling. Thus RET-independent GFRα1 is dispensable for organogenesis and nerve regeneration in vivo, indicating that trans-signaling and GFRα-dependent NCAM signaling play a minor role physiologically.
AB - The GDNF family ligands signal through a receptor complex composed of a ligand binding subunit, GFRα, and a signaling subunit, the RET tyrosine kinase. GFRαs are expressed not only in RET-expressing cells, but also in cells lacking RET. A body of evidence suggests that RET-independent GFRαs are important for (1) modulation of RET signaling in a non-cell-autonomous fashion (trans-signaling) and (2) regulation of NCAM function. To address the physiological significance of these roles, we generated mice specifically lacking RET-independent GFRα1. These mice exhibited no deficits in regions where trans-signaling has been implicated in vitro, including enteric neurons, motor neurons, kidney, and regenerating nerves. Furthermore, no abnormalities were found in the olfactory bulb, which requires proper NCAM function for its formation and is putatively a site of GDNF-GFRα-NCAM signaling. Thus RET-independent GFRα1 is dispensable for organogenesis and nerve regeneration in vivo, indicating that trans-signaling and GFRα-dependent NCAM signaling play a minor role physiologically.
UR - http://www.scopus.com/inward/record.url?scp=8844247987&partnerID=8YFLogxK
U2 - 10.1016/j.neuron.2004.10.032
DO - 10.1016/j.neuron.2004.10.032
M3 - Article
C2 - 15541311
AN - SCOPUS:8844247987
SN - 0896-6273
VL - 44
SP - 623
EP - 636
JO - Neuron
JF - Neuron
IS - 4
ER -