FGF as a target-derived chemoattractant for developing motor axons genetically programmed by the LIM code.
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.
Shirasaki
Ryuichi
R
Gene Expression Laboratory, The Salk Institute, 10010 North Torrey Pines Road, La Jolla, California 92037, USA.
Lewcock
Joseph W
JW
Lettieri
Karen
K
Pfaff
Samuel L
SL
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
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