Corticotropin-releasing hormone (CRH) has been shown to modulate dendritic development in hippocampus.Mitotic kinesin-like protein 1 (MKLP1) plays key roles in dendritic differentiation.In the present study, we examined the effects of CRH on MKLP1 expression in cultured hippocampal neurons and determine subsequent signaling pathways involved.CRH dose-dependently increased MKLP 1 mRNA and protein expression.This effect can be reversed by CRHR1 antagonist but not by CRHR2 antagonist.CRHtR1 knockdown impaired this effect of CRH.CRH stimulated GTP-bound Gαs protein and phosphorylated phospholipase C (PLC)-β3expression, which were blocked by CRHR1 antagonist.Transfection of GP antagonist-2A, an inhibitory peptide of Gαq protein, blocked CRH-induced phosphorylated PLC-β3 expression.PLC and PKC inhibitors completely blocked whereas AC and PKA inhibitors did not affect CRH-induced MKLP1 expression.Our results indicate that CRH act on CRHR1 to induce MKLP1 expression via PLC/PKC signaling pathway.CRH may regulate MKLP1 expression, thereby modulating dendritic development.