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Deficiency of MeCP2 leads to Rett syndrome, a severe neurodevelopmental disorder. We have previously shown that MeCP2 plays critical roles in the maturation step of new neurons during neurogenesis. MeCP2 is known to regulate the expression of brain-derived neurotrophic factor (BDNF), a potent neurotrophic factor for neuronal maturation. Nevertheless, how MeCP2 regulates BDNF expression and how MeCP2 deficiency leads to reduced BDNF expression remain unclear. Here, we show that MeCP2 regulates the expression of a microRNA, miR-15a. We find that miR-15a plays a significant role in the regulation of neuronal maturation. Overexpression of miR-15a inhibits dendritic morphogenesis in immature neurons. Conversely, a reduction in miR-15a has the opposite effect. We further show that miR-15a regulates expression levels of BDNF, and exogenous BDNF could partially rescue the neuronal maturation deficits resulting from miR-15a overexpression. Finally, inhibition of miR-15a could rescue neuronal maturation deficits in MeCP2-deficient adult-born new neurons. These results demonstrate a novel role for miR-15a in neuronal development and provide a missing link in the regulation of BDNF by MeCP2. Stem Cells \u00a02015;33:1618\u20131629<\/jats:p>","DOI":"10.1002\/stem.1950","type":"journal-article","created":{"date-parts":[[2015,1,13]],"date-time":"2015-01-13T23:48:30Z","timestamp":1421192910000},"page":"1618-1629","source":"Crossref","is-referenced-by-count":63,"title":["Inhibition of miR-15a Promotes BDNF Expression and Rescues Dendritic Maturation Deficits in MeCP2-Deficient Neurons"],"prefix":"10.1093","volume":"33","author":[{"given":"Yu","family":"Gao","sequence":"first","affiliation":[{"name":"Waisman Center School of Medicine and Public Health, Waisman Center, University of Wisconsin-Madison, Madison, Wisconsin, USA"},{"name":"Department of Neuroscience School of Medicine and Public Health, Waisman Center, University of Wisconsin-Madison, Madison, Wisconsin, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juan","family":"Su","sequence":"additional","affiliation":[{"name":"Waisman Center School of Medicine and Public Health, Waisman Center, University of Wisconsin-Madison, Madison, Wisconsin, USA"},{"name":"Department of Neuroscience School of Medicine and Public Health, Waisman Center, University of Wisconsin-Madison, Madison, Wisconsin, USA"},{"name":"Key Laboratory of Animal Physiology and Biochemistry Ministry of Agriculture College of Veterinary Medicine, Nanjing Agricultural University, Nanjing, Jiangsu, People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weixiang","family":"Guo","sequence":"additional","affiliation":[{"name":"Waisman Center School of Medicine and Public Health, Waisman Center, University of Wisconsin-Madison, Madison, Wisconsin, USA"},{"name":"Department of Neuroscience School of Medicine and Public Health, Waisman Center, University of Wisconsin-Madison, Madison, Wisconsin, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eric D.","family":"Polich","sequence":"additional","affiliation":[{"name":"Waisman Center School of Medicine and Public Health, Waisman Center, University of Wisconsin-Madison, Madison, Wisconsin, USA"},{"name":"Department of Neuroscience School of Medicine and Public Health, Waisman Center, University of Wisconsin-Madison, Madison, Wisconsin, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel P.","family":"Magyar","sequence":"additional","affiliation":[{"name":"Waisman Center School of Medicine and Public Health, Waisman Center, University of Wisconsin-Madison, Madison, Wisconsin, USA"},{"name":"Department of Neuroscience School of Medicine and Public Health, Waisman Center, University of Wisconsin-Madison, Madison, Wisconsin, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yina","family":"Xing","sequence":"additional","affiliation":[{"name":"Waisman Center School of Medicine and Public Health, Waisman Center, University of Wisconsin-Madison, Madison, Wisconsin, USA"},{"name":"Department of Neuroscience School of Medicine and Public Health, Waisman Center, University of Wisconsin-Madison, Madison, Wisconsin, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongda","family":"Li","sequence":"additional","affiliation":[{"name":"Waisman Center School of Medicine and Public Health, Waisman Center, University of Wisconsin-Madison, Madison, Wisconsin, USA"},{"name":"Department of Medical Genetics School of Medicine and Public Health, Waisman Center, University of Wisconsin-Madison, Madison, Wisconsin, USA"},{"name":"Department of Genetics School of Medicine and Public Health, Waisman Center, University of Wisconsin-Madison, Madison, Wisconsin, USA"},{"name":"Department of Neurology School of Medicine and Public Health, Waisman Center, University of Wisconsin-Madison, Madison, Wisconsin, USA"},{"name":"Genetics Training Program School of Medicine and Public Health, Waisman Center, University of Wisconsin-Madison, Madison, Wisconsin, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard D.","family":"Smrt","sequence":"additional","affiliation":[{"name":"Department of Neuroscience University of New Mexico School of Medicine, Albuquerque, New Mexico, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiang","family":"Chang","sequence":"additional","affiliation":[{"name":"Waisman Center School of Medicine and Public Health, Waisman Center, University of Wisconsin-Madison, Madison, Wisconsin, USA"},{"name":"Department of Medical Genetics School of Medicine and Public Health, Waisman Center, University of Wisconsin-Madison, Madison, Wisconsin, USA"},{"name":"Department of Genetics School of Medicine and Public Health, Waisman Center, University of Wisconsin-Madison, Madison, Wisconsin, USA"},{"name":"Department of Neurology School of Medicine and Public Health, Waisman Center, University of Wisconsin-Madison, Madison, Wisconsin, USA"},{"name":"Genetics Training Program School of Medicine and Public Health, Waisman Center, University of Wisconsin-Madison, Madison, Wisconsin, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinyu","family":"Zhao","sequence":"additional","affiliation":[{"name":"Waisman Center School of Medicine and Public Health, Waisman Center, University of Wisconsin-Madison, Madison, Wisconsin, USA"},{"name":"Department of Neuroscience School of Medicine and Public Health, Waisman Center, University of Wisconsin-Madison, Madison, Wisconsin, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2015,4,23]]},"reference":[{"key":"2022011103312641700_stem1950-bib-0001","doi-asserted-by":"crossref","first-page":"185","DOI":"10.1038\/13810","article-title":"Rett syndrome is caused by mutations in X-linked MECP2, encoding methyl- CpG-binding protein 2","volume":"23","author":"Amir","year":"1999","journal-title":"Nat 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