GDNF and neurturin are target-derived factors essential for cranial parasympathetic neuron development

Eri Hashino, M. Shero, D. Junghans, H. Rohrer, J. Milbrandt, Jr Johnson E.M.

Research output: Contribution to journalArticle

54 Citations (Scopus)

Abstract

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 GFRα1 and Ret, but not of GFRα2, in innervating ciliary ganglion neurons, the results also suggest that target-derived GDNF regulates the expression of its high-affinity coreceptors.

Original languageEnglish (US)
Pages (from-to)3773-3782
Number of pages10
JournalDevelopment (Cambridge)
Volume128
Issue number19
StatePublished - 2001
Externally publishedYes

Fingerprint

Neurturin
Parasympathetic Ganglia
Glial Cell Line-Derived Neurotrophic Factor
Neurons
Axons
Down-Regulation
Muscles
Neural Crest
Smooth Muscle
Cell Death

Keywords

  • Axon
  • Chicken
  • Ciliary ganglion
  • CNTF
  • GDNF
  • GFRα
  • Neurturin
  • Ret

ASJC Scopus subject areas

  • Anatomy
  • Cell Biology

Cite this

Hashino, E., Shero, M., Junghans, D., Rohrer, H., Milbrandt, J., & Johnson E.M., J. (2001). GDNF and neurturin are target-derived factors essential for cranial parasympathetic neuron development. Development (Cambridge), 128(19), 3773-3782.

GDNF and neurturin are target-derived factors essential for cranial parasympathetic neuron development. / Hashino, Eri; Shero, M.; Junghans, D.; Rohrer, H.; Milbrandt, J.; Johnson E.M., Jr.

In: Development (Cambridge), Vol. 128, No. 19, 2001, p. 3773-3782.

Research output: Contribution to journalArticle

Hashino, E, Shero, M, Junghans, D, Rohrer, H, Milbrandt, J & Johnson E.M., J 2001, 'GDNF and neurturin are target-derived factors essential for cranial parasympathetic neuron development', Development (Cambridge), vol. 128, no. 19, pp. 3773-3782.
Hashino, Eri ; Shero, M. ; Junghans, D. ; Rohrer, H. ; Milbrandt, J. ; Johnson E.M., Jr. / GDNF and neurturin are target-derived factors essential for cranial parasympathetic neuron development. In: Development (Cambridge). 2001 ; Vol. 128, No. 19. pp. 3773-3782.
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