title: Rho/Rho-kinase signaling pathway controls axon patterning of a specified subset of cranial motor neurons.
abstract: Cranial motor neurons, which are divided into somatic motor (SM), branchiomotor (BM) and visceral motor (VM) neurons, form distinct axonal trajectories to innervate their synapse targets. Rho GTPase regulates various neuronal functions through one of the major effector proteins, Rho-kinase. Here, we addressed the in vivo role of the Rho/Rho-kinase signaling pathway in axon patterning of cranial motor neurons. We performed conditional expression of a dominant-negative mutant for RhoA or Rho-kinase in transgenic mice by using the Cre-loxP system to suppress the activity of these molecules in developing cranial motor neurons. Blockade of the Rho/Rho-kinase signaling pathway caused defects in the patterning of SM axons but not in that of BM/VM axons, in which defects were accompanied by reduced muscle innervation and reduced synapse formation by SM neurons. In addition, blockade of the signaling pathway shifted the trajectory of growing SM axons in explant cultures, whereas it did not appear to affect the rate of spontaneous axonal outgrowth. These results indicate that the Rho/Rho-kinase signaling pathway plays an essential role in the axon patterning of cranial SM neurons during development.
authors.affiliation: Department of Molecular Genetics, Institute of Biomedical Sciences, Fukushima Medical University School of Medicine, Fukushima 960-1295, Japan. kazuto@fmu.ac.jp
authors.forename: Kenta
authors.initials: K
authors.lastname: Kobayashi
authors.forename: Tomoyuki
authors.initials: T
authors.lastname: Masuda
authors.forename: Masanori
authors.initials: M
authors.lastname: Takahashi
authors.forename: Jun-ichi
authors.initials: J
authors.lastname: Miyazaki
authors.forename: Masahiro
authors.initials: M
authors.lastname: Nakagawa
authors.forename: Motokazu
authors.initials: M
authors.lastname: Uchigashima
authors.forename: Masahiko
authors.initials: M
authors.lastname: Watanabe
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Yaginuma
authors.forename: Noriko
authors.initials: N
authors.lastname: Osumi
authors.forename: Kozo
authors.initials: K
authors.lastname: Kaibuchi
authors.forename: Kazuto
authors.initials: K
authors.lastname: Kobayashi
mesh_terms: D000818:Animals; D001369:Axons / Q000502:physiology* / Q000648:ultrastructure; D004622:Embryo, Mammalian / Q000033:anatomy & histology / Q000502:physiology; D051379:Mice; D008822:Mice, Transgenic; D009046:Motor Neurons / Q000166:cytology* / Q000502:physiology*; D055495:Neurogenesis / Q000502:physiology; D015398:Signal Transduction / Q000502:physiology*; D013569:Synapses / Q000502:physiology; D054460:rho-Associated Kinases / Q000235:genetics / Q000378:metabolism*; D020742:rhoA GTP-Binding Protein / Q000235:genetics / Q000378:metabolism*
chemical_list: D054460:rho-Associated Kinases; D020742:rhoA GTP-Binding Protein