TY - JOUR
T1 - Rho/Rho-kinase signaling pathway controls axon patterning of a specified subset of cranial motor neurons
AU - Kobayashi, Kenta
AU - Masuda, Tomoyuki
AU - Takahashi, Masanori
AU - Miyazaki, Jun ichi
AU - Nakagawa, Masahiro
AU - Uchigashima, Motokazu
AU - Watanabe, Masahiko
AU - Yaginuma, Hiroyuki
AU - Osumi, Noriko
AU - Kaibuchi, Kozo
AU - Kobayashi, Kazuto
PY - 2011/2
Y1 - 2011/2
N2 - 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.
AB - 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.
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U2 - 10.1111/j.1460-9568.2010.07554.x
DO - 10.1111/j.1460-9568.2010.07554.x
M3 - Article
C2 - 21219475
AN - SCOPUS:79951488645
SN - 0953-816X
VL - 33
SP - 612
EP - 621
JO - European Journal of Neuroscience
JF - European Journal of Neuroscience
IS - 4
ER -