DCC functions as an accelerator of thalamocortical axonal growth downstream of spontaneous thalamic activity

Controlling axon growth rate is a fundamental process when establishing brain connections. Using the thalamocortical system as a model, we previously showed that spontaneous calcium activity controls the growth rate of thalamocortical axons by regulating the transcription of Robo1 through an NF-kB binding site in its promoter. Robo1 acts as a brake for thalamocortical axons growth in vivo. Here, we have identified the Netrin-1 receptor DCC acting as an accelerator for thalamic axon growth. Dcc transcription is regulated by spontaneous calcium activity in thalamocortical neurons. Activating DCC signaling restores normal axon growth in electrically silenced neurons. Moreover, we have identified an AP-1 binding site in the Dcc promoter that is crucial for the activity-dependent regulation of this gene. In sum, we have determined Dcc gene as a novel downstream target of spontaneous calcium activity involved in axon growth control. Together with our previously published data, we demonstrate a mechanism for axon growth control that relies on the activity-dependent regulation of two functionally opposed molecules, Robo1 and DCC. Their activity will allow a tight and efficient regulation of this process necessary for the correct establishment of neuronal connections during development.