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Trio is a key guanine nucleotide exchange factor coordinating regulation of the migration and morphogenesis of granule cells in the developing cerebellum.


ABSTRACT: Orchestrated regulation of neuronal migration and morphogenesis is critical for neuronal development and establishment of functional circuits, but its regulatory mechanism is incompletely defined. We established and analyzed mice with neural-specific knock-out of Trio, a guanine nucleotide exchange factor with multiple guanine nucleotide exchange factor domains. Knock-out mice showed defective cerebella and severe signs of ataxia. Mutant cerebella had no granule cells in the internal granule cell layer due to aberrant granule cell migration as well as abnormal neurite growth. Trio-deficient granule cells showed reduced extension of neurites and highly branched and misguided processes with perturbed stabilization of actin and microtubules. Trio deletion caused down-regulation of the activation of Rac1, RhoA, and Cdc42, and mutant granule cells appeared to be unresponsive to neurite growth-promoting molecules such as Netrin-1 and Semaphorin 6A. These results suggest that Trio may be a key signal module for the orchestrated regulation of neuronal migration and morphogenesis during cerebellar development. Trio may serve as a signal integrator decoding extrinsic signals to Rho GTPases for cytoskeleton organization.

SUBMITTER: Peng YJ 

PROVIDER: S-EPMC2915719 | biostudies-literature | 2010 Aug

REPOSITORIES: biostudies-literature

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Trio is a key guanine nucleotide exchange factor coordinating regulation of the migration and morphogenesis of granule cells in the developing cerebellum.

Peng Ya-Jing YJ   He Wei-Qi WQ   Tang Jing J   Tao Tao T   Chen Chen C   Gao Yun-Qian YQ   Zhang Wen-Cheng WC   He Xue-Yan XY   Dai Yu-Yuan YY   Zhu Nian-Chun NC   Lv Ning N   Zhang Cheng-Hai CH   Qiao Yan-Ning YN   Zhao Li-Ping LP   Gao Xiang X   Zhu Min-Sheng MS  

The Journal of biological chemistry 20100601 32


Orchestrated regulation of neuronal migration and morphogenesis is critical for neuronal development and establishment of functional circuits, but its regulatory mechanism is incompletely defined. We established and analyzed mice with neural-specific knock-out of Trio, a guanine nucleotide exchange factor with multiple guanine nucleotide exchange factor domains. Knock-out mice showed defective cerebella and severe signs of ataxia. Mutant cerebella had no granule cells in the internal granule cel  ...[more]

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