Human Molecular Genetics Advance Access published online on October 7, 2004
Human Molecular Genetics, doi:10.1093/hmg/ddh309
© 2004 by Oxford University Press
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
1 Laboratory of Developmental Neuroendocrinology, Department of Endocrinology, Centre of Excellence on Neurodegenerative Diseases, University of Milano, Milano, Italy
* To whom correspondence should be addressed. E-mail: roberto.magi{at}unimi.it.
X-linked Kallmann's syndrome (KS) is a genetic disease characterised by anosmia and hypogonadism due to impairment in the development of olfactory axons and in the migration of Gonadotropin-Releasing Hormone (GnRH)-producing neurons. Deletions or point mutations of a gene located at Xp22.3 (KAL1) are responsible for the disease. This gene encodes for a secreted heparin binding-protein (KAL or anosmin-1) which exhibits similarities with cell-adhesion molecules. In the present study, we show for the first time a direct action of anosmin-1 on the migratory activity of GnRH neurons. Specifically, we exposed immortalised migrating GnRH neurons (GN11 cells) to conditioned media (CM) of COS or CHO cells transiently transfected with human KAL1 gene in microchemotaxis and collagen gel assays. We found that KAL-enriched media produced a cell-specific chemotactic response of GN11 cells. None of the CM enriched on three forms of anosmin-1 carrying different missense mutations (N267K, E514K, F517L) found in patients affected by X-linked KS, affected the chemomigration of GN11 cells. Anosmin binds to the GN11 cell surface by interacting with the heparan-sulphate proteoglycans and the chemotactic effect of anosmin-1-enriched CM can be specifically blocked by heparin or by heparinase pre-treatment. These results strongly suggest an involvement of anosmin-1 in the control of the migratory behavior of GnRH neurons and provide novel information on the pathogenesis of KS.
Article
The product of X-linked Kallmann's syndrome gene (KAL1) affects the migratory activity of Gonadotropin-Releasing Hormone (GnRH)-producing neurons
2 Telethon Institute for Genetic and Medicine (TIGEM), Naples, Italy; Laboratory of Genetics, The Salk Institute, La Jolla, CA, USA
3 Department of Human Morphology, University of Milano, Milano, Italy
4 Telethon Institute for Genetic and Medicine (TIGEM), Naples, Italy
5 Laboratory of Developmental Neuroendocrinology, Department of Endocrinology, Centre of Excellence on Neurodegenerative Diseases, University of Milano, Via G. Balzaretti, 9, 20133 Milano, Italy
Abstract 
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  L. M. Cotton, M. K. O'Bryan, and B. T. Hinton Cellular Signaling by Fibroblast Growth Factors (FGFs) and Their Receptors (FGFRs) in Male Reproduction Endocr. Rev., April 1, 2008; 29(2): 193 - 216. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 X. Zhu, A. S. Gleiberman, and M. G. Rosenfeld Molecular Physiology of Pituitary Development: Signaling and Transcriptional Networks Physiol Rev, July 1, 2007; 87(3): 933 - 963. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. M. Nielsen-Preiss, M. P. Allen, M. Xu, D. A. Linseman, J. E. Pawlowski, R. J. Bouchard, B. C. Varnum, K. A. Heidenreich, and M. E. Wierman Adhesion-Related Kinase Induction of Migration Requires Phosphatidylinositol-3-Kinase and Ras Stimulation of Rac Activity in Immortalized Gonadotropin-Releasing Hormone Neuronal Cells Endocrinology, June 1, 2007; 148(6): 2806 - 2814. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. Magni, E. Dozio, M. Ruscica, H. Watanobe, A. Cariboni, R. Zaninetti, M. Motta, and R. Maggi Leukemia Inhibitory Factor Induces the Chemomigration of Immortalized Gonadotropin-Releasing Hormone Neurons through the Independent Activation of the Janus Kinase/Signal Transducer and Activator of Transcription 3, Mitogen-Activated Protein Kinase/Extracellularly Regulated Kinase 1/2, and Phosphatidylinositol 3-Kinase/Akt Signaling Pathways Mol. Endocrinol., May 1, 2007; 21(5): 1163 - 1174. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. Bhagavath, N. Xu, M. Ozata, R. L. Rosenfield, D. P. Bick, R. J. Sherins, and L. C. Layman KAL1 mutations are not a common cause of idiopathic hypogonadotrophic hypogonadism in humans Mol. Hum. Reprod., March 1, 2007; 13(3): 165 - 170*. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Cariboni, J. Hickok, S. Rakic, W. Andrews, R. Maggi, S. Tischkau, and J. G. Parnavelas Neuropilins and Their Ligands Are Important in the Migration of Gonadotropin-Releasing Hormone Neurons J. Neurosci., February 28, 2007; 27(9): 2387 - 2395. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 F. Cerrato, J. Shagoury, M. Kralickova, A. Dwyer, J. Falardeau, M. Ozata, G. Van Vliet, P. Bouloux, J. E Hall, F. J Hayes, et al. Coding sequence analysis of GNRHR and GPR54 in patients with congenital and adult-onset forms of hypogonadotropic hypogonadism Eur. J. Endocrinol., November 1, 2006; 155(suppl_1): S3 - S10. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. B. Trarbach, E. M. F. Costa, B. Versiani, M. de Castro, M. T. M. Baptista, H. M. Garmes, B. B. de Mendonca, and A. C. Latronico Novel Fibroblast Growth Factor Receptor 1 Mutations in Patients with Congenital Hypogonadotropic Hypogonadism with and without Anosmia J. Clin. Endocrinol. Metab., October 1, 2006; 91(10): 4006 - 4012. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Okubo, F. Sakai, E. L. Lau, G. Yoshizaki, Y. Takeuchi, K. Naruse, K. Aida, and Y. Nagahama Forebrain Gonadotropin-Releasing Hormone Neuronal Development: Insights from Transgenic Medaka and the Relevance to X-Linked Kallmann Syndrome Endocrinology, March 1, 2006; 147(3): 1076 - 1084. [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]
|
|
|
|
 |
|
 A. Cariboni, S. Rakic, A. Liapi, R. Maggi, A. Goffinet, and J. G. Parnavelas Reelin provides an inhibitory signal in the migration of gonadotropin-releasing hormone neurons Development, November 1, 2005; 132(21): 4709 - 4718. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. Kim, S R Herrick, E Lemyre, S Kishikawa, J A Salisz, S Seminara, M E MacDonald, G A P Bruns, C C Morton, B J Quade, et al. Hypogonadotropic hypogonadism and cleft lip and palate caused by a balanced translocation producing haploinsufficiency for FGFR1 J. Med. Genet., August 1, 2005; 42(8): 666 - 672. [Full Text] [PDF]
|
|