Arhgef1 is expressed in cortical neural progenitor cells and regulates neurite outgrowth of newly differentiated neurons

• Published in: Neuroscience letters 2017-01, Vol.638, p.27-34
• Main Authors: Xiang, Xiaoliang, Zhuang, Xiaoji, Li, Shengnan, Shi, Lei
• Format: Article
• Language: English
• Subjects: Animals; Arhgef1; Cell Differentiation; Cerebral Cortex - cytology; Cerebral Cortex - embryology; Cerebral Cortex - metabolism; Gene Silencing; Mice, Inbred ICR; Neural progenitor cell; Neural Stem Cells - cytology; Neural Stem Cells - metabolism; Neurite outgrowth; Neurites - physiology; Neurons - cytology; Neurons - metabolism; Neurons - physiology; Primary Cell Culture; rho GTP-Binding Proteins - metabolism; Rho guanine nucleotide exchange factor; Rho Guanine Nucleotide Exchange Factors - genetics; Rho Guanine Nucleotide Exchange Factors - metabolism; RhoA
• ISSN: 0304-3940; 1872-7972
• DOI: 10.1016/j.neulet.2016.11.067

•The RhoGEF Arhgef1 is highly expressed in developing cortex and cortical neural progenitor cells.•Arhgef1 is expressed in newly differentiated cortical neurons but not astrocytes.•Arhgef1 expression is downregulated during neuronal differentiation.•Arhgef1 inhibits neurite outgrowth of newly differentiated neurons. Neurite outgrowth is crucial for the maturation of neurons and the establishment of anatomical connections during development of the nervous system. We report here that Arhgef1, a RhoA guanine nucleotide exchange factor previously found expressed in the early stages of neuronal development to regulate neurite outgrowth, is also highly expressed in cortical neural progenitor cells (NPCs). To better dissect its role in NPCs, we knocked down Arhgef1 expression in these cells and induced differentiated of them into neurons. Notably, silencing of Arhgef1 markedly enhanced neurite outgrowth in neurons derived from NPCs. Furthermore, we showed that Arhgef1 silencing inhibited the activity of RhoA, and pharmacological blockade of RhoA activity promoted neurite outgrowth in NPC-derived neurons. These findings reveal that Arhgef1 controls the process of neurite formation in newborn cortical neurons derived from NPCs.