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1 Center for Hearing and Deafness and
2 Department of Anatomy and Cell Biology, State University of New York at Buffalo, Buffalo, NY 14214, USA
3 Max-Planck-Institut für Hirnforschung, Deutschordenstrasse 46, D-60628 Frankfurt, Germany
4 Departments of Pathology and Internal Medicine,
5 Departments of Neurology, Molecular Biology and Pharmacology, Washington University School of Medicine, St. Louis, MO 63110, USA
*Author for correspondence (e-mail: hashino{at}acsu.buffalo.edu)
Accepted July 12, 2001
During development, parasympathetic ciliary ganglion neurons arise from the neural crest and establish synaptic contacts on smooth and striate muscle in the eye. The factors that promote the ciliary ganglion pioneer axons to grow toward their targets have yet to be determined. Here, we show that glial cell line-derived neurotrophic factor (GDNF) and neurturin (NRTN) constitute target-derived factors for developing ciliary ganglion neurons. Both GDNF and NRTN are secreted from eye muscle located in the target and trajectory pathway of ciliary ganglion pioneer axons during the period of target innervation. After this period, however, the synthesis of GDNF declines markedly, while that of NRTN is maintained throughout the cell death period. Furthermore, both in vitro and in vivo function-blocking of GDNF at early embryonic ages almost entirely suppresses ciliary axon outgrowth. These results demonstrate that target-derived GDNF is necessary for ciliary ganglion neurons to innervate ciliary muscle in the eye. Since the down-regulation of GDNF in the eye is accompanied by down-regulation of GFR
1 and Ret, but not of GFR2, in innervating ciliary ganglion neurons, the results also suggest that target-derived GDNF regulates the expression of its high-affinity coreceptors.
Key words: GDNF, Neurturin, CNTF, GFR, Ret, Ciliary ganglion, Axon, Chicken
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