title: Spontaneous activity regulates Robo1 transcription to mediate a switch in thalamocortical axon growth.
abstract: 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.
authors: Instituto de Neurociencias de Alicante, Universidad Miguel Hernández-Consejo Superior de Investigaciones Científicas, San't Joan d'Alacant, Spain.
authors: Erik
authors: E
authors: Mire
authors: Cecilia
authors: C
authors: Mezzera
authors: Eduardo
authors: E
authors: Leyva-Díaz
authors: Ana V
authors: AV
authors: Paternain
authors: Paola
authors: P
authors: Squarzoni
authors: Lisa
authors: L
authors: Bluy
authors: Mar
authors: M
authors: Castillo-Paterna
authors: María José
authors: MJ
authors: López
authors: Sandra
authors: S
authors: Peregrín
authors: Marc
authors: M
authors: Tessier-Lavigne
authors: Sonia
authors: S
authors: Garel
authors: Joan
authors: J
authors: Galcerán
authors: Juan
authors: J
authors: Lerma
authors: Guillermina
authors: G
authors: López-Bendito
mesh_terms: D000818:Animals; D001369:Axons / Q000473:pathology / Q000502:physiology*; D002118:Calcium / Q000378:metabolism; D020013:Calcium Signaling / Q000235:genetics*; D002540:Cerebral Cortex / Q000254:growth & development / Q000502:physiology*; D005260:Female; D018507:Gene Expression Regulation, Developmental / Q000235:genetics; D051379:Mice; D009419:Nerve Tissue Proteins / Q000235:genetics* / Q000502:physiology; D011971:Receptors, Immunologic / Q000235:genetics* / Q000502:physiology; D013788:Thalamus / Q000254:growth & development / Q000502:physiology*; D000097905:Roundabout Proteins
chemical_list: D002118:Calcium; D009419:Nerve Tissue Proteins; D011971:Receptors, Immunologic; D000097905:Roundabout Proteins; C120010:Slit1 protein, mouse