title: FARP1 promotes the dendritic growth of spinal motor neuron subtypes through transmembrane Semaphorin6A and PlexinA4 signaling.
abstract: The dendritic morphology of neurons dictates their abilities to process and transmit information; however, the signaling pathways that regulate dendritic growth and complexity are poorly understood. Here, we show that retinoids induce the expression of the FERM Rho-GEF protein FARP1 in the developing spinal cord. FARP1 is expressed in subsets of motor neurons and is enriched in dendrites of lateral motor column (LMC) neurons that innervate the limb. FARP1 is necessary and sufficient to promote LMC dendritic growth but does not affect dendrite number or axonal morphology. We show that FARP1 serves as a specific effector of transmembrane Semaphorin6A and PlexinA4 signals to regulate LMC dendritic growth, and that its Rho-GEF domain is necessary for this function. These findings reveal that retinoid and Sema6A/PlexA4 signaling pathways intersect through FARP1 to control dendritic growth, and uncover the existence of subtype-specific signaling networks that control dendritic developmental programs in spinal motor neurons.
authors.affiliation: The Solomon Snyder Department of Neuroscience, The Johns Hopkins University School of Medicine, 725 N. Wolfe Street, Baltimore, MD 21205, USA.
authors.forename: BinQuan
authors.initials: B
authors.lastname: Zhuang
authors.forename: YouRong Sophie
authors.initials: YS
authors.lastname: Su
authors.forename: Shanthini
authors.initials: S
authors.lastname: Sockanathan
mesh_terms: D000818:Animals; D030161:Avian Proteins / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism*; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology; D002462:Cell Membrane / Q000378:metabolism / Q000648:ultrastructure; D002642:Chick Embryo; D003598:Cytoskeletal Proteins / Q000235:genetics / Q000378:metabolism; D003712:Dendrites / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects / Q000502:physiology; D020662:Guanine Nucleotide Exchange Factors / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D009046:Motor Neurons / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D055495:Neurogenesis / Q000187:drug effects / Q000502:physiology; D017434:Protein Structure, Tertiary / Q000187:drug effects / Q000502:physiology; D011956:Receptors, Cell Surface / Q000235:genetics / Q000378:metabolism*; D012176:Retinoids / Q000378:metabolism / Q000494:pharmacology; D064067:Rho Guanine Nucleotide Exchange Factors; D039961:Semaphorins / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects / Q000235:genetics; D013116:Spinal Cord / Q000166:cytology / Q000378:metabolism*; D020741:rho GTP-Binding Proteins / Q000235:genetics / Q000378:metabolism
chemical_list: D030161:Avian Proteins; D003598:Cytoskeletal Proteins; C577227:FARP1 protein, human; D020662:Guanine Nucleotide Exchange Factors; C524474:Plxna4 protein, human; D011956:Receptors, Cell Surface; D012176:Retinoids; D064067:Rho Guanine Nucleotide Exchange Factors; C504201:SEMA6A protein, human; D039961:Semaphorins; D020741:rho GTP-Binding Proteins