Seminars
Abstract: During development, the central nervous system establishes precise connections with the body to coordinate organ function. A crucial component of communication between the brain and body is the vagus nerve (cranial nerve X), which innervates multiple organ systems including the heart, lungs and digestive tract to regulate blood pressure, heart rate, respiration and digestion. Despite this important role, the molecular mechanisms guiding the vagus nerve to these organ targets during development remain unknown. We have developed the zebrafish embryo as a powerful model for interrogating vagus nerve development, taking advantage of its optical clarity and genetic accessibility. Using a novel photoconversion-based retrograde axon tracing approach we show that vagal motor neurons (mXns) that project to different organs (e.g. gallbladder, stomach, intestines) are spatially segregated within the hindbrain vagus nucleus. We hypothesize that these distinct mXn "target groups" have distinct molecular identities that guide axon targeting. To test this hypothesis, we have generated a developmental scRNAseq atlas focused on cranial motor neurons and have validated the spatially restricted expression of transcription factors and cell-surface molecules within the vagus motor nucleus. We have generated genetic tools to correlate gene expression with target groups, and performing a reverse mutagenesis screen to test the role of these candidates in topographic map formation, revealing preliminary mXn identity phenotypes. We have also observed that mXn axons contact specific subsets of enteric neurons (ENS) during motor axon pathfinding and have begun testing the role of these contacts in guiding topographic motor targeting.
