QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

HOME  |   SEARCH  |   ARCHIVE  |   SUBSCRIBE  |   CONTACT  |   HELP

The Journal of Neuroscience, February 27, 2008, 28(9):2131-2146; doi:10.1523/JNEUROSCI.5185-07.2008

This Article Full Text Full Text (PDF) Supplemental Data Submit an eLetter Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Web of Science (7) Citing Articles via Google Scholar Google Scholar Articles by Gould, T. W. Articles by Enomoto, H. Search for Related Content PubMed PubMed Citation Articles by Gould, T. W. Articles by Enomoto, H.

 Previous Article  |  Next Article 

Development/Plasticity/Repair
The Neurotrophic Effects of Glial Cell Line-Derived Neurotrophic Factor on Spinal Motoneurons Are Restricted to Fusimotor Subtypes

Thomas W. Gould,¹ Shigenobu Yonemura,² Ronald W. Oppenheim,³ Shiho Ohmori,¹ and Hideki Enomoto¹

¹Laboratory for Neuronal Differentiation and Regeneration and ²Laboratory for Cellular Morphogenesis, RIKEN Center for Developmental Biology, Kobe 650-0047, Japan, and ³Department of Neurobiology and Anatomy and The Neuroscience Program, Wake Forest University School of Medicine, Winston-Salem, North Carolina 27103

Correspondence should be addressed to either of the following: Hideki Enomoto, Laboratory for Neuronal Differentiation and Regeneration, RIKEN Center for Developmental Biology, 2-2-3 Minatojima-Minamimachi, Chuo-ku, Kobe 650-0047, Japan, Email: enomoto{at}cdb.riken.jp; or Thomas W. Gould at his present address: Oceania University Building, National Health Complex, Moto'otua, P.O. Box 232, Apia, Samoa, E-mail: Email: tom.gould{at}oceaniamed.org

Glial cell line-derived neurotrophic factor (GDNF) regulates multiple aspects of spinal motoneuron (MN) development, including gene expression, target selection, survival, and synapse elimination, and mice lacking either GDNF or its receptors GDNF family receptor 1 (GFR1) and Ret exhibit a 25% reduction of lumbar MNs at postnatal day 0 (P0). Whether this loss reflects a generic trophic role for GDNF and thus a reduction of all MN subpopulations, or a more restricted role affecting only specific MN subpopulations, such as those innervating individual muscles, remains unclear. We therefore examined MN number and innervation in mice in which Ret, GFR1, or GDNF was deleted and replaced by reporter alleles. Whereas nearly all hindlimb muscles exhibited normal gross innervation, intrafusal muscle spindles displayed a significant loss of innervation in most but not all muscles at P0. Furthermore, we observed a dramatic and restricted loss of small myelinated axons in the lumbar ventral roots of adult mice in which the function of either Ret or GFR1 was inactivated in MNs early in development. Finally, we demonstrated that the period during which spindle-innervating MNs require GDNF for survival is restricted to early neonatal development, because mice in which the function of Ret or GFR1 was inactivated after P5 failed to exhibit denervation of muscle spindles or MN loss. Therefore, although GDNF influences several aspects of MN development, the survival-promoting effects of GDNF during programmed cell death are mostly confined to spindle-innervating MNs.

Key words: motoneuron; trophic; GDNF; fusimotor; innervation; axon; spindle; neuromuscular

---

Received Nov. 22, 2007; revised Dec. 18, 2007; accepted Dec. 31, 2007.

Correspondence should be addressed to either of the following: Hideki Enomoto, Laboratory for Neuronal Differentiation and Regeneration, RIKEN Center for Developmental Biology, 2-2-3 Minatojima-Minamimachi, Chuo-ku, Kobe 650-0047, Japan, Email: enomoto{at}cdb.riken.jp; or Thomas W. Gould at his present address: Oceania University Building, National Health Complex, Moto'otua, P.O. Box 232, Apia, Samoa, E-mail: Email: tom.gould{at}oceaniamed.org

This article has been cited by other articles:

				A. Friese, J. A. Kaltschmidt, D. R. Ladle, M. Sigrist, T. M. Jessell, and S. Arber Gamma and alpha motor neurons distinguished by expression of transcription factor Err3 PNAS, August 11, 2009; 106(32): 13588 - 13593. [Abstract] [Full Text] [PDF]

				T. W. Gould and H. Enomoto Neurotrophic Modulation of Motor Neuron Development Neuroscientist, February 1, 2009; 15(1): 105 - 116. [Abstract] [PDF]

Home  |   Search  |   Archive  |   Subscribe  |   Contact  |   Help