title: DCC functions as an accelerator of thalamocortical axonal growth downstream of spontaneous thalamic activity.
abstract: Controlling the axon growth rate is fundamental when establishing brain connections. Using the thalamocortical system as a model, we previously showed that spontaneous calcium activity influences the growth rate of thalamocortical axons by regulating the transcription of Robo1 through an NF-κB-binding site in its promoter. Robo1 acts as a brake on the growth of thalamocortical axons in vivo. Here, we have identified the Netrin-1 receptor DCC as an accelerator for thalamic axon growth. Dcc transcription is regulated by spontaneous calcium activity in thalamocortical neurons and activating DCC signaling restores normal axon growth in electrically silenced neurons. Moreover, we identified an AP-1-binding site in the Dcc promoter that is crucial for the activity-dependent regulation of this gene. In summary, we have identified the Dcc gene as a novel downstream target of spontaneous calcium activity involved in axon growth. Together with our previous data, we demonstrate a mechanism to control axon growth that relies on the activity-dependent regulation of two functionally opposed receptors, Robo1 and DCC. These two proteins establish a tight and efficient means to regulate activity-guided axon growth in order to correctly establish neuronal connections during development.
authors.affiliation: Instituto de Neurociencias de Alicante, Universidad Miguel Hernández-Consejo Superior de Investigaciones Científicas (UMH-CSIC), San Joan d'Alacant, Spain.
authors.forename: Mar
authors.initials: M
authors.lastname: Castillo-Paterna
authors.affiliation: Instituto de Neurociencias de Alicante, Universidad Miguel Hernández-Consejo Superior de Investigaciones Científicas (UMH-CSIC), San Joan d'Alacant, Spain.
authors.forename: Verónica
authors.initials: V
authors.lastname: Moreno-Juan
authors.affiliation: Instituto de Neurociencias de Alicante, Universidad Miguel Hernández-Consejo Superior de Investigaciones Científicas (UMH-CSIC), San Joan d'Alacant, Spain.
authors.forename: Anton
authors.initials: A
authors.lastname: Filipchuk
authors.affiliation: Instituto de Neurociencias de Alicante, Universidad Miguel Hernández-Consejo Superior de Investigaciones Científicas (UMH-CSIC), San Joan d'Alacant, Spain.
authors.forename: Luis
authors.initials: L
authors.lastname: Rodríguez-Malmierca
authors.affiliation: Instituto de Neurociencias de Alicante, Universidad Miguel Hernández-Consejo Superior de Investigaciones Científicas (UMH-CSIC), San Joan d'Alacant, Spain.
authors.forename: Rafael
authors.initials: R
authors.lastname: Susín
authors.affiliation: Instituto de Neurociencias de Alicante, Universidad Miguel Hernández-Consejo Superior de Investigaciones Científicas (UMH-CSIC), San Joan d'Alacant, Spain g.lbendito@umh.es.
authors.forename: Guillermina
authors.initials: G
authors.lastname: López-Bendito
mesh_terms: D000818:Animals; D001369:Axons / Q000502:physiology* / Q000648:ultrastructure; D001665:Binding Sites; D002118:Calcium / Q000378:metabolism; D002478:Cells, Cultured; D000075389:DCC Receptor; D004622:Embryo, Mammalian; D018507:Gene Expression Regulation, Developmental; D020439:Growth Cones / Q000502:physiology; D051379:Mice; D016328:NF-kappa B / Q000378:metabolism; D009414:Nerve Growth Factors / Q000378:metabolism; D000075388:Netrin-1; D009474:Neurons / Q000502:physiology; D011401:Promoter Regions, Genetic; D011956:Receptors, Cell Surface / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D015398:Signal Transduction; D013788:Thalamus / Q000166:cytology / Q000196:embryology / Q000502:physiology*; D025521:Tumor Suppressor Proteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*
chemical_list: D000075389:DCC Receptor; C501910:Dcc protein, mouse; D016328:NF-kappa B; D009414:Nerve Growth Factors; C000617353:Ntn1 protein, mouse; D011956:Receptors, Cell Surface; D025521:Tumor Suppressor Proteins; D000075388:Netrin-1; D002118:Calcium
keywords: Netrin‐1/Dcc signalling; axon growth; development; spontaneous activity; thalamus