title: FGF as a target-derived chemoattractant for developing motor axons genetically programmed by the LIM code.
abstract: LIM transcription factors confer developing axons with specific navigational properties, but the downstream guidance receptors and ligands are not well defined. The dermomyotome, a transient structure from which axial muscles arise, is the source of a secreted long-range chemoattractant specific for medial-class spinal motor neuron axons (MMCm axons). We show that fibroblast growth factors (FGFs) produced by the dermomyotome selectively attract MMCm axons in vitro. FGF receptor 1 (FGFR1) expression is restricted to MMCm neurons, and conditional deletion of FGFR1 causes motor axon guidance defects. Furthermore, reprogramming the identity of limb-innervating motor neurons to that of dermomyotome-innervating MMCm cells using the LIM factor Lhx3 induces FGFR1 expression and shifts an increased number of motor axons to an FGF-responsive state. These results point to a role for FGF signaling in axon guidance and further unravel how downstream effectors of LIM codes direct wiring of the developing nervous system.
authors.affiliation: Gene Expression Laboratory, The Salk Institute, 10010 North Torrey Pines Road, La Jolla, California 92037, USA.
authors.forename: Ryuichi
authors.initials: R
authors.lastname: Shirasaki
authors.forename: Joseph W
authors.initials: JW
authors.lastname: Lewcock
authors.forename: Karen
authors.initials: K
authors.lastname: Lettieri
authors.forename: Samuel L
authors.initials: SL
authors.lastname: Pfaff
mesh_terms: D000818:Animals; D001369:Axons / Q000502:physiology*; D002630:Chemotactic Factors / Q000096:biosynthesis / Q000235:genetics* / Q000502:physiology; D002645:Chickens; D018920:Coculture Techniques; D004622:Embryo, Mammalian; D004625:Embryo, Nonmammalian; D018507:Gene Expression Regulation, Developmental / Q000502:physiology*; D018398:Homeodomain Proteins / Q000096:biosynthesis / Q000235:genetics*; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D009046:Motor Neurons / Q000502:physiology*; D009924:Organ Culture Techniques; D051496:Receptor, Fibroblast Growth Factor, Type 1 / Q000096:biosynthesis / Q000235:genetics* / Q000502:physiology; D017468:Receptors, Fibroblast Growth Factor / Q000096:biosynthesis / Q000235:genetics; D014157:Transcription Factors / Q000096:biosynthesis / Q000235:genetics
chemical_list: D002630:Chemotactic Factors; D018398:Homeodomain Proteins; D017468:Receptors, Fibroblast Growth Factor; D014157:Transcription Factors; C496349:Fgfr1 protein, mouse; D051496:Receptor, Fibroblast Growth Factor, Type 1