Rett syndrome(RTT)is a progressive neurological disorder caused by mutations in the X-linked gene methyl-CpG-binding protein 2(MeCP2).The endogenous function of MeCP2 during neurogenesis is still unclear.Here we report that mecp2 is critical for neural development in zebrafish.mecp2 was broadly expressed initially in embryos and enriched later in the brain in zebrafish.Morpholino knockdown of mecp2 inhibited neuronal cell differentiation.Mechanistically,inhibitor of differentiation protein 1(id1)was upregulated in mecp2 morphants,consistent with the fact that excessive Id1 proteins suppress differentiation during neurogenesis.Furthermore,many her family genes were also upregulated in mecp2 morphants.Remarkably,knockdown id1 fully rescued neuronal differentiation in mecp2 morphants.Our study supports that MeCP2 plays an important role in neuronal development through the MeCP2-Id1/Hers axis and so provides new insights into molecular pathogenesis of RTT.