Chromatin signatures of neuronal subpopulations with divergent projection at the midline identify novel wiring regulators

Resumen del póster presentado al 19th Meeting Spanish Society of Neuroscience (SENC), celebrado en Lleida del 3 al 5 de noviembre de 2021.Therapeutic approaches aimed to restore the function of damaged neuronal circuits will benefit from a better understanding of the mechanisms driving and constraining circuit assembly. The binary decision of crossing or avoiding the midline that retinal ganglion cells (RGCs) axons take at the optic chiasm during embryonic development is essential for binocular vision and represents a simple and robust model to identify novel mechanisms controlling axon guidance decisions during circuits formation. By comparing the transcriptome and chromatin occupancy profiles of crossed and uncrossed RGCs, we identified key differences between these two populations of neurons. Our unbiased screens revealed important differences in the expression of guidance molecules and the binding of transcription factors to regulatory regions, exposing novel transcriptional mechanisms underlying axon guidance decisions. Functional in vivo experiments with candidate genes validate this approach and reveal the implication of several transcription factors, such as the Lhx family, in the navigation of RGC axons. Overall, our study retrieved novel factors controlling axon guidance, thereby contributing to a better understanding of the transcriptional regulatory logic underlying neuronal connectivity.Peer reviewe