MicroRNAs are Necessary for BMP-7-induced Dendritic Growth in Cultured Rat Sympathetic Neurons
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ORIGINAL RESEARCH
MicroRNAs are Necessary for BMP‑7‑induced Dendritic Growth in Cultured Rat Sympathetic Neurons Kristina Pravoverov1 · Katherine Whiting1 · Slesha Thapa1 · Trevor Bushong1 · Karen Trang1 · Pamela J. Lein2 · Vidya Chandrasekaran1 Received: 12 December 2018 / Accepted: 14 May 2019 © Springer Science+Business Media, LLC, part of Springer Nature 2019
Abstract Neuronal connectivity is dependent on size and shape of the dendritic arbor. However, mechanisms controlling dendritic arborization, especially in the peripheral nervous system, are not completely understood. Previous studies have shown that bone morphogenetic proteins (BMPs) are important initiators of dendritic growth in peripheral neurons. In this study, we examined the hypothesis that post-transcriptional regulation mediated by microRNAs (miRNAs) is necessary for BMP-7-induced dendritic growth in these neurons. To examine the role of miRNAs in BMP-7-induced dendritic growth, microarray analyses was used to profile miRNA expression in cultured sympathetic neurons from the superior cervical ganglia of embryonic day 21 rat pups at 6 and 24 h after treatment with BMP-7 (50 ng/mL). Our data showed that BMP-7 significantly regulated the expression of 43 of the 762 miRNAs. Of the 43 miRNAs, 22 showed robust gene expression; 14 were upregulated by BMP-7 and 8 were downregulated by BMP-7. The expression profile for miR-335, miR-664-1*, miR-21, and miR-23b was confirmed using qPCR analyses. Functional studies using morphometric analyses of dendritic growth in cultured sympathetic neurons transfected with miRNA mimics and inhibitors indicated that miR-664-1*, miR-23b, and miR-21 regulated early stages of BMP-7-induced dendritic growth. In summary, our data provide evidence for miRNA-mediated post-transcriptional regulation as important downstream component of BMP-7 signaling during early stages of dendritic growth in sympathetic neurons. Keywords MicroRNA · Dendrite · Bone morphogenetic proteins · Sympathetic neurons
Introduction Dendrites are the primary sites of synapse formation in the nervous system, and the extent of the dendritic arbor correlates directly with synaptic density (Purves 1975; Purves and Hume 1981; Rubin 1985; Purves and Lichtman 1985) and tonic activity (De Castro et al. 1995). Changes in the number of dendrites and the size of the dendritic arbor are associated with neurodegenerative disease and neurodevelopmental disorders, including Alzheimer’s disease, Down’s syndrome, Rett’s syndrome, autism, and schizophrenia (Comery et al. 1997; Kaufmann and Moser 2000; Pardo and Eberhart 2007; * Vidya Chandrasekaran vc5@stmarys‑ca.edu 1
Department of Biology, Saint Mary’s College of California, 1928 Saint Mary’s Road, Moraga, CA 94556, USA
Department of Molecular Biosciences, University of California, 1089 Veterinary Medicine Drive, Davis, CA 95616, USA
2
Garey 2010; Penzes et al. 2011; Kulkarni and Firestein 2012; Supekar et al. 2013; Copf 2016). Therefore, understanding the mechanisms that influence the size and complexity of
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