A rapid and dynamic regulation of GDNF-family ligands and receptors correlate with the developmental dependency of cutaneous sensory innervation

Glial cell line-derived neurotrophic factor (GDNF) and neurturin (NTN) are members of the transforming growth factor-P family and have been shown to e licit neurotrophic effects upon several classes of neurons including dopami nergic neurons, motoneurons, parasympathetic, sympathetic as well as primar y sensory neurons. However, there is little information available on their roles in cutaneous innervation. Herein, we have studied the regulation of g dnf, ntn and the GDNF family receptors and examined their role in the devel opment of facial cutaneous innervation in GDNF mutant mice. A dynamic spati al and temporal regulation of gdnf, ntn and their ligand binding receptors within the follicle-sinus complex correlate with development of distinct su bclasses of sensory nerve endings. Furthermore, development of NGF-dependen t myelinated mechanoreceptors, i.e. reticular and transverse lanceolate end ings also require GDNF during ending formation and maintenance. In addition , ligand and receptor association seems to be intricately linked to a local Schwann cell-axon interaction essential for sensory terminal formation. Ou r results suggests that functionally specified nerve endings depend on diff erent GDNF family members and that in contrast to neurotrophins, this famil y of neurotrophic factors may be acting at local sites of terminal Schwann cell-axon growth cone interactions and that they collaborate with neurotrop hins by supporting the same populations of neurons but at different times i n development.