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

HOME  |   SEARCH  |   ARCHIVE  |   SUBSCRIBE  |   CONTACT  |   HELP

The Journal of Neuroscience, March 23, 2005, 25(12):3142-3150; doi:10.1523/JNEUROSCI.4759-04.2005

This Article Full Text Full Text (PDF) 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 ISI 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 ISI Web of Science (9) Citing Articles via Google Scholar Google Scholar Articles by Gamble, J. A. Articles by Herbison, A. E. Search for Related Content PubMed PubMed Citation Articles by Gamble, J. A. Articles by Herbison, A. E.

 Previous Article  |  Next Article 

Development/Plasticity/Repair
Disruption of Ephrin Signaling Associates with Disordered Axophilic Migration of the Gonadotropin-Releasing Hormone Neurons

John A. Gamble,¹ Delicia K. Karunadasa,¹ Jean-Rémi Pape,¹ Michael J. Skynner,¹ Martin G. Todman,¹ R. John Bicknell,¹ Jeremy P. Allen,¹ and Allan E. Herbison^1,2

¹Neurobiology Programme, The Babraham Institute, Cambridge CB2 4AT, United Kingdom, and ²Centre for Neuroendocrinology and Department of Physiology, University of Otago School of Medical Sciences, Dunedin 9001, New Zealand

Ephrin signaling is involved in repulsive and attractive interactions mediating axon guidance and cell-boundary formation in the developing nervous system. As a result of a fortuitous transgene integration event, we have identified here a potential role for EphA5 in the axophilic migration of gonadotropin-releasing hormone (GnRH) neurons from the nasal placode into the brain along ephrin-expressing vomeronasal axons. Transgene integration in the GNR23 mouse line resulted in a 26 kb deletion in chromosome 5, 67 kb 3' to Epha5. This induced a profound, region-specific upregulation of EphA5 mRNA and protein expression in the developing mouse brain. The GnRH neurons in GNR23 mice overexpressed EphA5 from embryonic day 11, whereas ephrin A3 and A5 mRNA levels in olfactory neurons were unchanged. The GnRH neurons were found to be slow in commencing their migration from the olfactory placode and also to form abnormal clusters of cells on the olfactory axons, prohibiting their migration out of the nose. As a result, adult hemizygous mice had only 40% of the normal complement of GnRH neurons in the brain, whereas homozygous mice had <15%. This resulted in infertility in adult female homozygous GNR23 mice, suggesting that some cases of human hypogonadotropic hypogonadism may result from ephrin-related mutations. These data provide evidence for a role of EphA-ephrin signaling in the axophilic migration of the GnRH neurons during embryogenesis.

Key words: GnRH; ephrin; migration; embryogenesis; transgenic; lhrh

---

Received Nov 21, 2004; revised February 10, 2005; accepted February 11, 2005.

This article has been cited by other articles:

				A. E. Herbison, R. Porteous, J.-R. Pape, J. M. Mora, and P. R. Hurst Gonadotropin-Releasing Hormone Neuron Requirements for Puberty, Ovulation, and Fertility Endocrinology, February 1, 2008; 149(2): 597 - 604. [Abstract] [Full Text] [PDF]

				T. Cogliati, P. Delgado-Romero, E. R. Norwitz, J. Guduric-Fuchs, U. B. Kaiser, S. Wray, and I. R. Kirsch Pubertal Impairment in Nhlh2 Null Mice Is Associated with Hypothalamic and Pituitary Deficiencies Mol. Endocrinol., December 1, 2007; 21(12): 3013 - 3027. [Abstract] [Full Text] [PDF]

				P. Giacobini, A. Messina, S. Wray, C. Giampietro, T. Crepaldi, P. Carmeliet, and A. Fasolo Hepatocyte Growth Factor Acts as a Motogen and Guidance Signal for Gonadotropin Hormone-Releasing Hormone-1 Neuronal Migration J. Neurosci., January 10, 2007; 27(2): 431 - 445. [Abstract] [Full Text] [PDF]

				G. A. Schwarting, T. R. Henion, J. D. Nugent, B. Caplan, and S. Tobet Stromal cell-derived factor-1 (chemokine C-X-C motif ligand 12) and chemokine C-X-C motif receptor 4 are required for migration of gonadotropin-releasing hormone neurons to the forebrain. J. Neurosci., June 21, 2006; 26(25): 6834 - 6840. [Abstract] [Full Text] [PDF]

				S. A. Tobet and G. A. Schwarting Minireview: Recent Progress in Gonadotropin-Releasing Hormone Neuronal Migration Endocrinology, March 1, 2006; 147(3): 1159 - 1165. [Abstract] [Full Text] [PDF]

Home  |   Search  |   Archive  |   Subscribe  |   Contact  |   Help