Temporal control of axonal floor plate crossing through a combination of incoherent feedforward and feedback loops of gene regulatory network regulating Robo3 expression.

ABSTRACT: Spinal commissural neurons play a fundamental role in motor control and sensory perception. Robo3, a receptor expressed on pre-crossing commissural axons, is required for midline crossing. Its downregulation in post-crossing axons is essential for forming synapses with contralateral CNS targets. We demonstrate that, at the transcriptional level, the dynamic expression of Robo3 in pre-crossing neurons is controlled by incoherent feed-forward loops (iFFLs) and negative feedback loops (NFLs) that precisely regulate its transience and thereby determine midline crossing. Lhx2 and Lhx9 activate Robo3 while also inducing its repressor, Barhl2. Additionally, negative feedback loops fine-tune the transience of Robo3 expression by adjusting the relative strength of the activatio

SUBMITTER: Sudakevitz-Merzbach R 

PROVIDER: S-EPMC12636605 | biostudies-literature | 2025 Oct

REPOSITORIES: biostudies-literature