title: Establishing the trochlear motor axon trajectory: role of the isthmic organiser and Fgf8.
abstract: Formation of the trochlear nerve within the anterior hindbrain provides a model system to study a simple axonal projection within the vertebrate central nervous system. We show that trochlear motor neurons are born within the isthmic organiser and also immediately posterior to it in anterior rhombomere 1. Axons of the most anterior cells follow a dorsal projection, which circumnavigates the isthmus, while those of more posterior trochlear neurons project anterodorsally to enter the isthmus. Once within the isthmus, axons form large fascicles that extend to a dorsal exit point. We investigated the possibility that the projection of trochlear axons towards the isthmus and their subsequent growth within that tissue might depend upon chemoattraction. We demonstrate that both isthmic tissue and Fgf8 protein are attractants for trochlear axons in vitro, while ectopic Fgf8 causes turning of these axons away from their normal routes in vivo. Both inhibition of FGF receptor activation and inhibition of Fgf8 function in vitro affect formation of the trochlear projection within explants in a manner consistent with a guidance function of Fgf8 during trochlear axon navigation.
authors.affiliation: MRC Centre for Developmental Neurobiology, King's College London, Guy's Campus, 4 Floor New Hunt's House, UK. carol.irving@kcl.ac.uk
authors.forename: Carol
authors.initials: C
authors.lastname: Irving
authors.forename: Amar
authors.initials: A
authors.lastname: Malhas
authors.forename: Sarah
authors.initials: S
authors.lastname: Guthrie
authors.forename: Ivor
authors.initials: I
authors.lastname: Mason
mesh_terms: D000818:Animals; D001369:Axons / Q000502:physiology; D002630:Chemotactic Factors / Q000378:metabolism; D002642:Chick Embryo; D018920:Coculture Techniques; D046508:Culture Techniques; D004622:Embryo, Mammalian / Q000502:physiology; D051524:Fibroblast Growth Factor 8; D005346:Fibroblast Growth Factors / Q000494:pharmacology / Q000502:physiology*; D017403:In Situ Hybridization; D008953:Models, Anatomic; D009046:Motor Neurons / Q000166:cytology / Q000378:metabolism / Q000502:physiology*; D051381:Rats; D012249:Rhombencephalon / Q000166:cytology* / Q000196:embryology / Q000378:metabolism; D014321:Trochlear Nerve / Q000196:embryology* / Q000254:growth & development
chemical_list: D002630:Chemotactic Factors; C496458:Fgf8 protein, rat; D051524:Fibroblast Growth Factor 8; D005346:Fibroblast Growth Factors