Soluble and bound forms of GFRα1 elicit different GDNF‐independent neurite growth responses in primary sensory neurons

Abstract

We have investigated the role of glial cell‐line derived neurotrophic factor (GDNF) and the effect of soluble or immobilized localization of its GDNF family receptor α1 (GFRα1) on neurite growth in cultured embryonic Bax^−/− dorsal root ganglion neurons, which survive in the absence of trophic support. Whereas GDNF alone has a moderate effect on neurite growth, soluble and immobilized GFRα1 elicit opposing and GDNF‐independent effects on neurite growth by a phospholipase C (PLC) γ‐dependent mechanism. Thus, GFRα1 elicits nerve growth responses independent of GDNF. However, GDNF in the presence of soluble or immobilized GFRα1 reverse the GDNF‐independent GFRα1 modulation of neurite growth. The different outcome of soluble and bound GFRα1 combined with our previous immunohistochemical data showing GFRα1‐protein in Schwann cells but not axons suggest terminal Schwann cells as a source of locally administered target‐derived GFRα1 and place this receptor in the path of axonal growth and guidance. Thus, target‐derived GFRα1 play opposing roles when presented alone and with GDNF and, therefore, can function as a nerve growth cue that both can promote and prevent growth in the developing peripheral nervous system. Developmental Dynamics 227:27–34, 2003