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The Journal of Neuroscience, October 1, 1999, 19(19):8476-8486

Multiple Actions of Neurturin Correlate with Spatiotemporal Patterns of Ret Expression in Developing Chick Cranial Ganglion Neurons

Eri Hashino^{1, 2}, Eugene M. Johnson Jr³, Jeffrey Milbrandt⁴, Marlene Shero², Richard J. Salvi², and Christopher S. Cohan^{1, 2}

¹ Department of Anatomy and Cell Biology and ² Center for Hearing and Deafness, State University of New York at Buffalo, Buffalo, New York 14214, and Departments of ³ Neurology, Molecular Biology, and Pharmacology and ⁴  Pathology and Internal Medicine, Washington University School of Medicine, St. Louis, Missouri 63110

The neurotrophic effects of neurturin (NRTN) on chick cranial ganglia were evaluated at various embryonic stages in vitro and related to its receptor expression. NRTN promoted the outgrowth and survival of ciliary ganglion neurons at early embryonic (E) stages (E6-E12), trigeminal ganglion neurons at midstages (E9-E16), and vestibular ganglion neurons at late stages (E12-E16). NRTN had no positive effects on cochlear ganglion neurons throughout development. In accordance with the time and order of onset in NRTN responsiveness, Ret protein was first detected in ciliary ganglia at E6, subsequently in trigeminal ganglia at E9, and in vestibular ganglia at E12. Ret was absent in E16 ciliary ganglia as well as in cochlear ganglia at all developmental stages that were tested. Exogenous application of retinoic acid induced NRTN responsiveness and Ret protein expression from E9 vestibular ganglion neurons, suggesting that retinoic acid can regulate Ret protein expression in peripheral sensory neurons in vitro. Ret was confined to the neuron cell body, whereas GFR was localized predominantly in peripheral and central neurite processes. No noticeable change in GFR expression was seen in any cranial ganglia throughout the developmental stages that were tested (E6-E16). These results demonstrate that NRTN exerts neurotrophic effects on different cranial ganglia at different developmental stages and that the onset and offset of NRTN responsiveness are regulated mainly by the spatiotemporal patterns of Ret, but not of GFR receptors. The results also substantiate the recently emerging view that NRTN may be an essential target-derived neurotrophic factor for parasympathetic neurons during development.

Key words: neurturin; GFR; Ret; ciliary; trigeminal; vestibular; cochlear; chicken

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Copyright © 1999 Society for Neuroscience  0270-6474/99/19198476-11$05.00/0

This article has been cited by other articles:

				J. E. Pitera, V. V. Smith, A. S. Woolf, and P. J. Milla Embryonic Gut Anomalies in a Mouse Model of Retinoic Acid-Induced Caudal Regression Syndrome : Delayed Gut Looping, Rudimentary Cecum, and Anorectal Anomalies Am. J. Pathol., December 1, 2001; 159(6): 2321 - 2329. [Abstract] [Full Text] [PDF]

				E. Hashino, M. Shero, D. Junghans, H. Rohrer, J. Milbrandt, and E. M. Johnson Jr. GDNF and neurturin are target-derived factors essential for cranial parasympathetic neuron development Development, October 1, 2001; 128(19): 3773 - 3782. [Abstract] [Full Text] [PDF]

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