MiRNA-128 regulates the proliferation and neurogenesis of neural precursors by targeting PCM1 in the developing cortex
Wei Zhang,
Paul Jong Kim,
Zhongcan Chen,
Hidayat Lokman,
Lifeng Qiu,
Ke Zhang,
Steven George Rozen,
Eng King Tan,
Hyunsoo Shawn Je,
Li Zeng
Affiliations
Wei Zhang
Neural Stem Cell Research Lab, Research Department, National Neuroscience Institute, Singapore, Singapore
Paul Jong Kim
Molecular Neurophysiology Laboratory, Signature Program in Neuroscience and Behavioral Disorders, Duke-NUS Graduate Medical School, Singapore, Singapore
Zhongcan Chen
Neural Stem Cell Research Lab, Research Department, National Neuroscience Institute, Singapore, Singapore
Hidayat Lokman
Molecular Neurophysiology Laboratory, Signature Program in Neuroscience and Behavioral Disorders, Duke-NUS Graduate Medical School, Singapore, Singapore
Lifeng Qiu
Neural Stem Cell Research Lab, Research Department, National Neuroscience Institute, Singapore, Singapore
Ke Zhang
Neural Stem Cell Research Lab, Research Department, National Neuroscience Institute, Singapore, Singapore
Steven George Rozen
Center for Computational Biology, Duke-NUS Graduate Medical School, Singapore, Singapore
Eng King Tan
Department of Neurology, National Neuroscience Institute, Singapore, Singapore; Neuroscience and Behavioral Disorders program, Duke-NUS Graduate Medical School, Singapore, Singapore
Molecular Neurophysiology Laboratory, Signature Program in Neuroscience and Behavioral Disorders, Duke-NUS Graduate Medical School, Singapore, Singapore; Neuroscience and Behavioral Disorders program, Duke-NUS Graduate Medical School, Singapore, Singapore; Department of Physiology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
Li Zeng
Neural Stem Cell Research Lab, Research Department, National Neuroscience Institute, Singapore, Singapore; Neuroscience and Behavioral Disorders program, Duke-NUS Graduate Medical School, Singapore, Singapore
During the development, tight regulation of the expansion of neural progenitor cells (NPCs) and their differentiation into neurons is crucial for normal cortical formation and function. In this study, we demonstrate that microRNA (miR)-128 regulates the proliferation and differentiation of NPCs by repressing pericentriolar material 1 (PCM1). Specifically, overexpression of miR-128 reduced NPC proliferation but promoted NPC differentiation into neurons both in vivo and in vitro. In contrast, the reduction of endogenous miR-128 elicited the opposite effects. Overexpression of miR-128 suppressed the translation of PCM1, and knockdown of endogenous PCM1 phenocopied the observed effects of miR-128 overexpression. Furthermore, concomitant overexpression of PCM1 and miR-128 in NPCs rescued the phenotype associated with miR-128 overexpression, enhancing neurogenesis but inhibiting proliferation, both in vitro and in utero. Taken together, these results demonstrate a novel mechanism by which miR-128 regulates the proliferation and differentiation of NPCs in the developing neocortex.
