title: The branchial arches and HGF are growth-promoting and chemoattractant for cranial motor axons.
abstract: During development, cranial motor neurons extend their axons along distinct pathways into the periphery. For example, branchiomotor axons extend dorsally to leave the hindbrain via large dorsal exit points. They then grow in association with sensory ganglia, to their targets, the muscles of the branchial arches. We have investigated the possibility that pathway tissues might secrete diffusible chemorepellents or chemoattractants that guide cranial motor axons, using co-cultures in collagen gels. We found that explants of dorsal neural tube or hindbrain roof plate chemorepelled cranial motor axons, while explants of cranial sensory ganglia were weakly chemoattractive. Explants of branchial arch mesenchyme were strongly growth-promoting and chemoattractive for cranial motor axons. Enhanced and oriented axon outgrowth was also elicited by beads loaded with Hepatocyte Growth Factor (HGF); antibodies to this protein largely blocked the outgrowth and orientation effects of the branchial arch on motor axons. HGF was expressed in the branchial arches, whilst Met, which encodes an HGF receptor, was expressed by subpopulations of cranial motor neurons. Mice with targetted disruptions of HGF or Met showed defects in the navigation of hypoglossal motor axons into the branchial region. Branchial arch tissue may thus act as a target-derived factor that guides motor axons during development. This influence is likely to be mediated partly by Hepatocyte Growth Factor, although a component of branchial arch-mediated growth promotion and chemoattraction was not blocked by anti-HGF antibodies.
authors.affiliation: Centre for Developmental Neurobiology, King's College, Guy's Campus, London SE1 9RT, UK.
authors.forename: A
authors.initials: A
authors.lastname: Caton
authors.forename: A
authors.initials: A
authors.lastname: Hacker
authors.forename: A
authors.initials: A
authors.lastname: Naeem
authors.forename: J
authors.initials: J
authors.lastname: Livet
authors.forename: F
authors.initials: F
authors.lastname: Maina
authors.forename: F
authors.initials: F
authors.lastname: Bladt
authors.forename: R
authors.initials: R
authors.lastname: Klein
authors.forename: C
authors.initials: C
authors.lastname: Birchmeier
authors.forename: S
authors.initials: S
authors.lastname: Guthrie
mesh_terms: D000818:Animals; D001369:Axons / Q000502:physiology*; D001921:Brain / Q000166:cytology*; D001934:Branchial Region / Q000378:metabolism*; D002455:Cell Division; D002630:Chemotactic Factors / Q000235:genetics / Q000378:metabolism*; D002642:Chick Embryo; D018920:Coculture Techniques; D017950:Ganglia, Sensory; D015870:Gene Expression; D018390:Gene Targeting; D017228:Hepatocyte Growth Factor / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D018878:Limb Buds; D051379:Mice; D009046:Motor Neurons / Q000502:physiology*; D019859:Proto-Oncogene Proteins c-met / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D013131:Spine
chemical_list: D002630:Chemotactic Factors; D017228:Hepatocyte Growth Factor; D019859:Proto-Oncogene Proteins c-met