Spontaneous activity regulates Robo1 transcription to mediate a switch in thalamocortical axon growth
| Autor: | Guillermina López-Bendito, Sonia Garel, Joan Galcerán, Erik Mire, Eduardo Leyva-Díaz, Marc Tessier-Lavigne, Cecilia Mezzera, Sandra Peregrín, Juan Lerma, Paola Squarzoni, Lisa Bluy, Ana V. Paternain, Mar Castillo-Paterna, María José López |
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| Rok vydání: | 2012 |
| Předmět: |
Cerebral Cortex
General Neuroscience Gene Expression Regulation Developmental chemistry.chemical_element Nerve Tissue Proteins Calcium Biology Axons Transplantation Mice Thalamus nervous system chemistry ROBO1 Live cell imaging Transcription (biology) SLIT1 Transcriptional regulation Animals Female Calcium Signaling Receptors Immunologic Binding site Neuroscience |
| Zdroj: | Digital.CSIC. Repositorio Institucional del CSIC instname |
| Popis: | Developing axons must control their growth rate to follow the appropriate pathways and establish specific connections. However, the regulatory mechanisms involved remain elusive. By combining live imaging with transplantation studies in mice, we found that spontaneous calcium activity in the thalamocortical system and the growth rate of thalamocortical axons were developmentally and intrinsically regulated. Indeed, the spontaneous activity of thalamic neurons governed axon growth and extension through the cortex in vivo. This activity-dependent modulation of growth was mediated by transcriptional regulation of Robo1 through an NF-κB binding site. Disruption of either the Robo1 or Slit1 genes accelerated the progression of thalamocortical axons in vivo, and interfering with Robo1 signaling restored normal axon growth in electrically silent neurons. Thus, modifications to spontaneous calcium activity encode a switch in the axon outgrowth program that allows the establishment of specific neuronal connections through the transcriptional regulation of Slit1 and Robo1 signaling. © 2012 Nature America, Inc. All rights reserved. This work was supported by grants from the Spanish Ministerio de Ciencia e Innovación (BFU2006-07138 to J.L. and BFU2009-08261 to G.L.-B.), an Human Frontier Science Program Organization grant (RGP29/2008), the Consolider programme (CSD2007-00023) and an European Research Council grant (ERC-2009-StG_20081210 to G.L.-B.). |
| Databáze: | OpenAIRE |
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