POSTPONED Guidance mechanisms during neural circuit development

Status: This talk is in preparation - details may change

This lecture is postponed due to Coronavirus travel restrictions.

The vertebrate spinal cord contains a variety of longitudinally projecting axon tracts that transmit information from the brain to the periphery and vice versa. We had previously shown that the ephrinB-Eph signaling system controls the formation of both descending and ascending tracts during development. This work led to the identification of a population of excitatory dorsal spinal neurons marked by co-expression of the transcription factor Zic2 and the guidance receptor EphA4. We show that Zic2 neurons contribute to the dorsal column projection that transmits touch information from the spinal cord to the brain. I will review our work on Zic2 neurons integrating sensory feedback with information from the brain to generate appropriate motor movements. EphrinB-Eph signaling mediates contact repulsion at axon intermediate targets and involves a process termed trogocytosis, a form of intercellular cannibalism distinct from phagocytosis. I will briefly review our recent work on this topic that suggests that ephrin/Eph-induced trogocytosis uses phagocytosis-like mechanisms.

The FLRT family of adhesion molecules have the unique properties of acting as adhesion molecules and as repellents by binding to different partner proteins. Previously, we have shown that genetic ablation of FLRT1 and FLRT3 in mice leads to the development of macroscopic cortical folds during embryogenesis in a process independent of progenitor cell amplification. I will review our work indicating that intercellular adhesion of migrating cortical neurons is a key factor of cortical folding across species. I will finish by summarizing recent work on FLRTs and their partner proteins Teneurins and Latrophilins. Our results suggest that this synaptogenic protein complex is used for repulsive cell guidance during embryonic cortex development.