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.
Publication types
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Comparative Study
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Axons / physiology*
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Chemotactic Factors / biosynthesis
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Chemotactic Factors / genetics*
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Chemotactic Factors / physiology
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Chickens
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Coculture Techniques
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Embryo, Mammalian
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Embryo, Nonmammalian
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Gene Expression Regulation, Developmental / physiology*
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Homeodomain Proteins / biosynthesis
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Homeodomain Proteins / genetics*
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Mice
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Mice, Knockout
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Mice, Transgenic
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Motor Neurons / physiology*
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Organ Culture Techniques
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Receptor, Fibroblast Growth Factor, Type 1 / biosynthesis
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Receptor, Fibroblast Growth Factor, Type 1 / genetics*
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Receptor, Fibroblast Growth Factor, Type 1 / physiology
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Receptors, Fibroblast Growth Factor / biosynthesis
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Receptors, Fibroblast Growth Factor / genetics
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Transcription Factors / biosynthesis
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Transcription Factors / genetics
Substances
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Chemotactic Factors
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Homeodomain Proteins
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Receptors, Fibroblast Growth Factor
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Transcription Factors
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Fgfr1 protein, mouse
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Receptor, Fibroblast Growth Factor, Type 1