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.
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
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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.
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Communicated by B.G. Herrmann
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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
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DOI: https://doi.org/10.1007/s00427-006-0125-0