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.
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- Supplementary Text and Figures (17M)
Supplementary Figures 1–9
- Supplementary Video 1 (4M)
Speed of growth of TCA travelling at the vTel.
- Supplementary Video 2 (7M)
Speed of growth of TCA extending at the neocortex.
- Supplementary Video 3 (4M)
Speed of growth of TCA travelling at the angle at the PSPB.
- Supplementary Video 4 (1M)
Speed of growth of TCA travelling at the entrance of the neocortex.
- Supplementary Video 5 (6M)
Spontaneous activity in the thalamus of E12.5 embryo.
- Supplementary Video 6 (7M)
Spontaneous activity in the thalamus of E16.5 embryo.
- Supplementary Video 7 (4M)
Spontaneous activity in early thalamocortical growth cones.
- Supplementary Video 8 (4M)
Spontaneous activity in late thalamocortical growth cones.