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Front Cell Neurosci. 2016 Mar 31;10:85. doi: 10.3389/fncel.2016.00085. eCollection 2016.

Porf-2 Inhibits Neural Stem Cell Proliferation Through Wnt/β-Catenin Pathway by Its GAP Domain.

Author information

1
Department of Neurosurgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine Shanghai, China.
2
Neuroscience Division, Department of Anatomy, Histology, and Embryology, Shanghai Jiao Tong University School of Medicine Shanghai, China.
3
Department of Neurosurgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of MedicineShanghai, China; Institute of Traumatic Medicine, Shanghai Jiao Tong University School of MedicineShanghai, China.

Abstract

Neural stem cell (NSC) proliferation and differentiation play a pivotal role in the development of brain, the plasticity of the brain network, and the repair for brain function in CNS diseases. The mechanisms regulating NSC behavior are not well elucidated. Previous studies showed porf-2 functions as a modulator in central nerve system development. We here show that porf-2, a conserved family of RhoGAPs, is highly and specifically expressed in NSCs. We also demonstrate that porf-2 inhibits the proliferation of NSCs in vivo and in vitro, but has no effect on NSC differentiation. We investigated which domain is required for the role of porf-2 on NSC proliferation. By using neurosphere formation and Edu assay we confirmed the GAP domain is necessary for its function. In addition, we surveyed a few classical pathways on NSC proliferation and found that porf-2 inhibits NSC proliferation by suppressing the β-catenin nuclear translocation. Taken together, we show for the first time that porf-2 inhibits NSC proliferation through Wnt/β-catenin pathway by its GAP domain.

KEYWORDS:

GAP; cell proliferation; neural stem cell; porf-2; wnt/β-catenin signaling

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