Anosmin-1 stimulates outgrowth and branching of developing Purkinje axons.
During development, Purkinje axons elongate along precise trajectories and acquire stereotypic branching patterns to innervate targets in the deep nuclei and cerebellar cortex. These processes are accomplished through cell-intrinsic mechanisms, whose operation is regulated by environmental signaling cues. Here, we show that Anosmin-1, the protein defective in the X-linked form of Kallmann syndrome, is one among such cues. Anosmin-1, that stimulates axon elongation and branching in the olfactory system, is expressed by Purkinje cells and deep nuclear neurons of the rat cerebellum during the ontogenetic period when Purkinje axons acquire their mature pattern. These neurons also express the putative Anosmin-1 receptor, fibroblast growth factor receptor 1. Application of Anosmin-1 to dissociated cultures of embryonic (embryonic day 17, E17) or postnatal (postnatal day 0, P0) rat cerebellar cells enhances neuritic elongation and exerts a strong promoting action on the budding of collateral branches and on the extension of terminal arbors. Opposite effects are observed when neutralizing anti-Anosmin-1 antibodies are applied to the same cultures. Comparable results are obtained by administering the protein or the blocking antibodies to organotypic cultures of postnatal (P0) rat cerebellum. In P10 cerebellar slices, Anosmin-1 does not enhance the spontaneous regenerative capabilities of severed Purkinje axons, but promotes the terminal outgrowth of injured neurites into embryonic neocortical explants apposed to the axotomy site. Although Anosmin-1 is unable to change the overall intrinsic growth competence of Purkinje cells, it exerts a powerful stimulatory action on the budding and extension of collateral branches and terminal plexus, contributing to the patterning of Purkinje axons.
Gianola
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S
Department of Neuroscience and "Rita Levi Montalcini Centre for Brain Repair," Section of Physiology, National Institute of Neuroscience, University of Turin, Corso Raffaello, 30, I-10125 Turin, Italy.
de Castro
F
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Rossi
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F
D000704:Analysis of Variance; D000818:Animals; D000831:Animals, Newborn; D000906:Antibodies / Q000494:pharmacology; D001369:Axons / Q000187:drug effects* / Q000502:physiology; D019771:Axotomy / Q000379:methods; D002452:Cell Count / Q000379:methods; D002478:Cells, Cultured; D002531:Cerebellum / Q000166:cytology / Q000196:embryology / Q000254:growth & development; D006224:Cricetinae; D003412:Cricetulus; D004622:Embryo, Mammalian; D016326:Extracellular Matrix Proteins / Q000276:immunology / Q000378:metabolism / Q000494:pharmacology*; D018507:Gene Expression Regulation, Developmental / Q000502:physiology*; D006801:Humans; D009363:Neoplasm Proteins; D009419:Nerve Tissue Proteins / Q000276:immunology / Q000378:metabolism / Q000494:pharmacology*; D009924:Organ Culture Techniques; D011689:Purkinje Cells / Q000187:drug effects*; D051381:Rats; D017208:Rats, Wistar; D051496:Receptor, Fibroblast Growth Factor, Type 1 / Q000378:metabolism
C076266:ANOS1 protein, human; D000906:Antibodies; D016326:Extracellular Matrix Proteins; D009363:Neoplasm Proteins; D009419:Nerve Tissue Proteins; C068304:Wfdc18 protein, rat; C496350:Fgfr1 protein, rat; D051496:Receptor, Fibroblast Growth Factor, Type 1