Abstract
Kallmann syndrome is a genetically heterogeneous developmental disease characterised by a partial or complete lack of olfactory bulb development. Two genes underlying this disease have so far been identified: the KAL-1 gene, which encodes anosmin-1, an extracellular matrix protein that promotes axonal guidance and branch formation in vitro; and KAL-2, which encodes the known FGFR1. The implication of FGFR1 and anosmin-1 in the same developmental disease led us to test whether anosmin-1 and FGFR1 interact during the development of the olfactory system. In this paper, we showed that the two proteins co-localise in the olfactory bulb during development in rat. Using cross-immunoprecipitation assays of olfactory bulb extracts, we also demonstrated that anosmin-1 and FGFR1 are comprised within the same protein complex. Moreover, we show that anosmin-1 expression in CHO transfected cells increases FGFR1 accumulation, suggesting that anosmin-1 may act as a positive extracellular regulator of FGFR1 signalling. Taken together, our findings strongly suggest that anosmin-1 is an essential component of a FGFR1 pathway that plays a key role during olfactory bulb morphogenesis.
This is a preview of subscription content, log in via an institution to check access.
Abbreviations
- WAP:
-
whey acidic protein
- FNIII:
-
fibronectin type III repeat
- ECM:
-
extracellular matrix
- FGF:
-
fibroblast growth factor
- FGFR1:
-
fibroblast growth factor receptor 1
- HS:
-
heparan sulphate
- PGHS:
-
heparan sulphate glycosaminoglycan chain of a proteoglycan
References
Ardouin O, Legouis R, Fasano L, David-Watine B, Korn H, Hardelin J, Petit C (2000) Characterization of the two zebrafish orthologues of the KAL-1 gene underlying X chromosome-linked Kallmann syndrome. Mech Dev 90:89–94
Bulow HE, Berry KL, Topper LH, Peles E, Hobert O (2002) Heparan sulfate proteoglycan-dependent induction of axon branching and axon misrouting by the Kallmann syndrome gene kal-1. Proc Natl Acad Sci USA 99:6346–6351
de Morsier G (1955) Etudes sur les dysraphies crânio-encéphaliques. 1. Agénésie des lobes olfactifs (telencephaloschizis lateral) et des commissures calleuse et antérieure (telencephaloschizis median). La dysplasie olfacto-génitale. Schweiz Arch Neurol Psychiat 74:309–361
Dode C, Levilliers J, Dupont JM, De Paepe A, Le Du N, Soussi-Yanicostas N, Coimbra RS, Delmaghani S, Compain-Nouaille S, Baverel F, Pecheux C, Le Tessier D, Cruaud C, Delpech M, Speleman F, Vermeulen S, Amalfitano A, Bachelot Y, Bouchard P, Cabrol S, Carel JC, Delemarre-van de Waal H, Goulet-Salmon B, Kottler ML, Richard O, Sanchez-Franco F, Saura R, Young J, Petit C, Hardelin JP (2003) Loss-of-function mutations in FGFR1 cause autosomal dominant Kallmann syndrome. Nat Genet 33:463–465
Franco B, Guioli S, Pragliola A, Incerti B, Bardoni B, Tonlorenzi R, Carrozzo R, Maestrini E, Pieretti M, Taillon-Miller P et al (1991) A gene deleted in Kallmann’s syndrome shares homology with neural cell adhesion and axonal path-finding molecules. Nature 353:529–536
Hardelin JP, Julliard AK, Moniot B, Soussi-Yanicostas N, Verney C, Schwanzel-Fukuda M, Ayer-Le Lievre C, Petit C (1999) Anosmin-1 is a regionally restricted component of basement membranes and interstitial matrices during organogenesis: implications for the developmental anomalies of X chromosome-linked Kallmann syndrome. Dev Dyn 215:26–44
Hebert JM, Lin M, Partanen J, Rossant J, McConnell SK (2003) FGF signaling through FGFR1 is required for olfactory bulb morphogenesis. Development 130:1101–1111
Kallman FJ, Schoenfeld WA, Barrera SE (1944) The genetic aspects of primary eunuchoidism. Am J Ment Defic XLVII:203–236
Legouis R, Hardelin JP, Levilliers J, Claverie JM, Compain S, Wunderle V, Millasseau P, Le Paslier D, Cohen D, Caterina D et al (1991) The candidate gene for the X-linked Kallmann syndrome encodes a protein related to adhesion molecules. Cell 67:423–435
Maestre de San Juan A (1856) Falta total de los nervios olfactorios con anosmia en un individuo en quien existia una atrofia congénita de los testiculos y miembro viril. Siglo Medico 131:211
Naftolin F, Harris GW, Bobrow M (1971) Effect of purified luteinizing hormone releasing factor on normal and hypogonadotrophic anosmic men. Nature 232:496–497
Pellegrini L (2001) Role of heparan sulfate in fibroblast growth factor signalling: a structural view. Curr Opin Struct Biol 11:29–34
Ropiquet F, Giri D, Kwabi-Addo B, Mansukhani A, Ittmann M (2000) Increased expression of fibroblast growth factor 6 in human prostatic intraepithelial neoplasia and prostate cancer. Cancer Res 60:4245–4250
Schlessinger J (2000) Cell signaling by receptor tyrosine kinases. Cell 103:211–225
Schwanzel-Fukuda M, Bick D, Pfaff DW (1989) Luteinizing hormone-releasing hormone (LHRH)-expressing cells do not migrate normally in an inherited hypogonadal (Kallmann) syndrome. Brain Res Mol Brain Res 6:311–326
Soussi-Yanicostas N, Hardelin JP, Arroyo-Jimenez MM, Ardouin O, Legouis R, Levilliers J, Traincard F, Betton JM, Cabanie L, Petit C (1996) Initial characterization of anosmin-1, a putative extracellular matrix protein synthesized by definite neuronal cell populations in the central nervous system. J Cell Sci 109:1749–1757
Soussi-Yanicostas N et al (1998) Anosmin-1 underlying the X chromosome-linked Kallmann syndrome is an adhesive molecule that can modulate neurite growth in a cell-type specific manner. J Cell Sci 111:2953–2965
Soussi-Yanicostas N, de Castro F, Julliard AK, Perfettini I, Chedotal A, Petit C (2002) Anosmin-1, defective in the X-linked form of Kallmann syndrome, promotes axonal branch formation from olfactory bulb output neurons. Cell 109:217–228
Vassar R, Chao SK, Sitcheran R, Nunez JM, Vosshall LB, Axel R (1994) Topographic organization of sensory projections to the olfactory bulb. Cell 79:981–991
Zou Z, Horowitz LF, Montmayeur JP, Snapper S, Buck LB (2001) Genetic tracing reveals a stereotyped sensory map in the olfactory cortex. Nature 414:173–179
Acknowledgements
We thank C. Petit for her help. This work was supported by INSERM Avenir program grant No. R04190SP, Fondation pour la Recherche Médicale (FRM No. INE20050303379), and Fondation NRJ de l’Institut de France.
Author information
Authors and Affiliations
Corresponding author
Additional information
Communicated by B.G. Herrmann
Rights and permissions
About this article
Cite this article
Ayari, B., Soussi-Yanicostas, N. FGFR1 and anosmin-1 underlying genetically distinct forms of Kallmann syndrome are co-expressed and interact in olfactory bulbs. Dev Genes Evol 217, 169–175 (2007). https://doi.org/10.1007/s00427-006-0125-0
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00427-006-0125-0