PMID- 24431455 OWN - NLM STAT- MEDLINE DCOM- 20140313 LR - 20220510 IS - 1529-2401 (Electronic) IS - 0270-6474 (Print) IS - 0270-6474 (Linking) VI - 34 IP - 3 DP - 2014 Jan 15 TI - BDNF promotes axon branching of retinal ganglion cells via miRNA-132 and p250GAP. PG - 969-79 LID - 10.1523/JNEUROSCI.1910-13.2014 [doi] AB - A crucial step in the development of the vertebrate visual system is the branching of retinal ganglion cell (RGC) axons within their target, the superior colliculus/tectum. A major player in this process is the neurotrophin brain-derived neurotrophic factor (BDNF). However, the molecular basis for the signaling pathways mediating BDNF action is less well understood. As BDNF exerts some of its functions by controlling the expression of microRNAs (miRNAs), we investigated whether miRNAs are also involved in BDNF-mediated retinal axon branching. Here, we demonstrate that the expression pattern of miRNA-132 in the retina is consistent with its involvement in this process, and that BDNF induces the upregulation of miRNA-132 in retinal cultures. Furthermore, in vitro gain-of-function and loss-of-function approaches in retinal cultures reveal that miRNA-132 mediates axon branching downstream of BDNF. A known target of miRNA-132 is the Rho family GTPase-activating protein, p250GAP. We find that p250GAP is expressed in RGC axons and mediates the effects of miRNA-132 in BDNF-induced branching. BDNF treatment or overexpression of miRNA-132 leads to a reduction in p250GAP protein levels in retinal cultures, whereas the overexpression of p250GAP abolishes BDNF-induced branching. Finally, we used a loss-of-function approach to show that miRNA-132 affects the maturation of RGC termination zones in the mouse superior colliculus in vivo, while their topographic targeting remains intact. Together, our data indicate that BDNF promotes RGC axon branching during retinocollicular/tectal map formation via upregulation of miRNA-132, which in turn downregulates p250GAP. FAU - Marler, Katharine J AU - Marler KJ AD - MRC Centre for Developmental Neurobiology, King's College London, London SE1 1UL, United Kingdom, Department of Neurosurgery, Yale University School of Medicine, New Haven, Connecticut 06520-8082, and Department of Cell Biology, Harvard Medical School, Boston, Massachusetts 02115. FAU - Suetterlin, Philipp AU - Suetterlin P FAU - Dopplapudi, Asha AU - Dopplapudi A FAU - Rubikaite, Aine AU - Rubikaite A FAU - Adnan, Jihad AU - Adnan J FAU - Maiorano, Nicola A AU - Maiorano NA FAU - Lowe, Andrew S AU - Lowe AS FAU - Thompson, Ian D AU - Thompson ID FAU - Pathania, Manav AU - Pathania M FAU - Bordey, Angelique AU - Bordey A FAU - Fulga, Tudor AU - Fulga T FAU - Van Vactor, David L AU - Van Vactor DL FAU - Hindges, Robert AU - Hindges R FAU - Drescher, Uwe AU - Drescher U LA - eng GR - G0901899/MRC_/Medical Research Council/United Kingdom GR - BB/E015522/1/BB_/Biotechnology and Biological Sciences Research Council/United Kingdom GR - 089611/WT_/Wellcome Trust/United Kingdom GR - 083205/WT_/Wellcome Trust/United Kingdom GR - WT_/Wellcome Trust/United Kingdom GR - R01 NS069695/NS/NINDS NIH HHS/United States GR - G0902418/MRC_/Medical Research Council/United Kingdom PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - United States TA - J Neurosci JT - The Journal of neuroscience : the official journal of the Society for Neuroscience JID - 8102140 RN - 0 (ARHGAP32 protein, human) RN - 0 (Brain-Derived Neurotrophic Factor) RN - 0 (GTPase-Activating Proteins) RN - 0 (MIRN132 microRNA, mouse) RN - 0 (MicroRNAs) SB - IM MH - Animals MH - Axons/drug effects/*metabolism MH - Brain-Derived Neurotrophic Factor/*pharmacology MH - Cells, Cultured MH - Chick Embryo MH - Female MH - GTPase-Activating Proteins/deficiency/*physiology MH - Mice MH - Mice, Inbred C57BL MH - MicroRNAs/*physiology MH - Pregnancy MH - Retinal Ganglion Cells/drug effects/*metabolism PMC - PMC3891972 OTO - NOTNLM OT - BDNF OT - axon branching OT - axon guidance OT - miRNA OT - p250GAP OT - retinotectal projection EDAT- 2014/01/17 06:00 MHDA- 2014/03/14 06:00 PMCR- 2014/07/15 CRDT- 2014/01/17 06:00 PHST- 2014/01/17 06:00 [entrez] PHST- 2014/01/17 06:00 [pubmed] PHST- 2014/03/14 06:00 [medline] PHST- 2014/07/15 00:00 [pmc-release] AID - 34/3/969 [pii] AID - 1910-13 [pii] AID - 10.1523/JNEUROSCI.1910-13.2014 [doi] PST - ppublish SO - J Neurosci. 2014 Jan 15;34(3):969-79. doi: 10.1523/JNEUROSCI.1910-13.2014.