title: Myo9b and RICS modulate dendritic morphology of cortical neurons.
abstract: Regulated growth and branching of dendritic processes is critical for the establishment of neuronal circuitry and normal brain functions. Rho family GTPases, including RhoA, Rac1, and Cdc42, play a prominent role in dendritic development. RhoA inhibits dendritic branching and growth, whereas Rac1/Cdc42 does the opposite. It has been suggested that the activity of RhoA must be kept low to allow dendritic growth. However, how neurons restrict the activation of RhoA for proper dendritic development is not clear. In the present study, we undertook a comprehensive loss-of-function analysis of putative RhoA GTPase-activating proteins (RhoA GAPs) in the cortical neurons. The expression of 16 RhoA GAPs was detected in the developing rat brain, and RNA interference experiments suggest that 2 of them, Myo9b and RICS, are critical regulators of dendritic morphogenesis. Knockdown of either Myo9b or RICS in cultured cortical neurons or developing cortex resulted in decreased dendrite length and number. Inhibition of RhoA/ROCK signaling restores the defects of dendritic morphology induced by knockdown of Myo9b or RICS. These data demonstrate that Myo9b and RICS repress RhoA/Rock signaling and modulate dendritic morphogenesis in cortical neurons, providing evidence for critical physiological function of RhoA GAPs in regulation of dendritic development.
authors.affiliation: The State Key Laboratory of Medical Neurobiology and Pharmacology Research Center, Shanghai Medical College and Institutes of Brain Science, Fudan University, Shanghai 200032, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Long
authors.forename: Xinru
authors.initials: X
authors.lastname: Zhu
authors.forename: Ping
authors.initials: P
authors.lastname: Yang
authors.forename: Qinqin
authors.initials: Q
authors.lastname: Gao
authors.forename: Yuejun
authors.initials: Y
authors.lastname: Chen
authors.forename: Lan
authors.initials: L
authors.lastname: Ma
mesh_terms: D000818:Animals; D048429:Cell Size; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology* / Q000378:metabolism*; D003712:Dendrites / Q000378:metabolism* / Q000648:ultrastructure*; D009218:Myosins / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000502:physiology; D014018:Tissue Distribution; D054460:rho-Associated Kinases / Q000378:metabolism*; D020742:rhoA GTP-Binding Protein / Q000378:metabolism*
chemical_list: C113469:myosin IXB; D054460:rho-Associated Kinases; D009218:Myosins; D020742:rhoA GTP-Binding Protein