title: N-myc is a key switch regulating the proliferation cycle of postnatal cerebellar granule cell progenitors.
abstract: N-myc plays an important role in early cerebellar development; however, the role of N-myc in postnatal cerebellar development is still unknown. In this study, inducible and reversible N-myc mouse models (Nmyc(TRE/TRE):tTS and Nmyc(EGFP/TRE):tTS) are used to regulate and track the expression of endogenous N-myc in vivo. Loss of N-myc at the neonatal stage results in reduced proliferation of granule cell precursors (GCPs) and reduced cerebellar volume/mass. Restoration of N-myc expression no later than postnatal day 4 can rescue the cerebellar developmental defect caused by the absence of N-myc after birth. During cerebellar postnatal development, N-myc acts as a key switch, regulating the proliferation cycle of postnatal granule cell progenitors. Loss of N-myc significantly impairs the Sonic hedgehog signalling pathway, and disrupts the expression of cell cycle effectors with a significant reduction of Ccnd2. More importantly, N-myc negatively regulates the expression of microRNA-9 during postnatal cerebellar development. Our findings demonstrate that over-expression of miR-9 can inhibit the proliferation of GCPs. The regulation of these factors by N-myc is at least partly responsible for the switch role of N-myc in the proliferation cycle of GCPs.
authors.affiliation: School of Life Science and Technology, Tongji University. Shanghai 200092, China.
authors.forename: Ming
authors.initials: M
authors.lastname: Ma
authors.affiliation: Shanghai Research Center for Model Organisms, Shanghai 201203, China.
authors.forename: Wenting
authors.initials: W
authors.lastname: Wu
authors.affiliation: School of Life Science and Technology, Tongji University. Shanghai 200092, China.
authors.forename: Qing
authors.initials: Q
authors.lastname: Li
authors.affiliation: School of Life Science and Technology, Tongji University. Shanghai 200092, China.
authors.forename: Jinya
authors.initials: J
authors.lastname: Li
authors.affiliation: School of Life Science and Technology, Tongji University. Shanghai 200092, China.
authors.forename: Zhejin
authors.initials: Z
authors.lastname: Sheng
authors.affiliation: School of Life Science and Technology, Tongji University. Shanghai 200092, China.
authors.forename: Jiahao
authors.initials: J
authors.lastname: Shi
authors.affiliation: School of Life Science and Technology, Tongji University. Shanghai 200092, China.
authors.forename: Mengjie
authors.initials: M
authors.lastname: Zhang
authors.affiliation: School of Life Science and Technology, Tongji University. Shanghai 200092, China.
authors.forename: Hua
authors.initials: H
authors.lastname: Yang
authors.affiliation: Shanghai Research Center for Model Organisms, Shanghai 201203, China.
authors.forename: Zhugang
authors.initials: Z
authors.lastname: Wang
authors.affiliation: Shanghai Research Center for Model Organisms, Shanghai 201203, China.
authors.forename: Ruilin
authors.initials: R
authors.lastname: Sun
authors.affiliation: School of Life Science and Technology, Tongji University. Shanghai 200092, China.
authors.forename: Jian
authors.initials: J
authors.lastname: Fei
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D002453:Cell Cycle; D002454:Cell Differentiation; D049109:Cell Proliferation; D002531:Cerebellum / Q000166:cytology / Q000254:growth & development / Q000378:metabolism*; D056742:Cyclin D2 / Q000235:genetics* / Q000378:metabolism; D003594:Cytoplasmic Granules / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D053823:Hedgehog Proteins / Q000235:genetics* / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism; D058953:Neural Stem Cells / Q000166:cytology / Q000378:metabolism*; D009474:Neurons / Q000166:cytology / Q000378:metabolism*; D016271:Proto-Oncogene Proteins c-myc / Q000172:deficiency / Q000235:genetics*; D015398:Signal Transduction
chemical_list: C486196:Ccnd2 protein, mouse; D056742:Cyclin D2; D053823:Hedgehog Proteins; C551804:MIRN9 microRNA, mouse; D035683:MicroRNAs; D016271:Proto-Oncogene Proteins c-myc; C465570:Shh protein, mouse