The Roles of Pioneer Neurons and Adhesion Molecules in Neuronal Migration

University Of Chicago, Chicago IL

Investigators

Abstract

Nerves, the major communication pathways of our brain and spinal cord, are made of many individual communication fibers called axons. Each axon carries information from one single nerve cell (neuron). As an embryo develops, these fibers have to connect up correctly in order to make working neural circuits. Before these connections can form, the neurons have to move from the place they are born to the location where they will perform their role. Previously, the Principal Investigators have studied this process in the facial nerve, which controls facial expressions, and found that a single "pioneer" neuron guides the movement of the remaining neurons to their final destinations. Where do pioneer neurons come from, how do they know where to go, and how do other neurons know how to follow them? This project will address these questions in developing zebrafish embryos (animals with facial nerves similar to humans). Zebrafish embryos are transparent, and the experiments use specially-engineered zebrafish whose facial neurons are fluorescently labeled to make their cell migration visible. Experiments will also examine the roles of particular molecules found on the cell surface that are important for cell migration (cell adhesion molecules). A new kind of 3-dimensional imaging (light sheet microscopy) will be used to measure cell movements, and new software will be developed to visualize and analyze cell movement data. Once developed and tested at the University of Chicago and the Marine Biological Laboratory, these software tools will be made freely available. The project will additionally provide training opportunities for high school, undergraduate and graduate students; introduce elementary and middle school students to research; and engage the public via interactive displays at the Museum of Science and Industry (MSI). Subsets of neurons migrate tangentially within the neuroepithelial plane, often over significant distances. To better understand mechanisms underlying tangential migration that are important for neural circuit formation, this project focuses on facial branchiomotor neurons (FBMNs), which undergo a tangential migration that is conserved in vertebrates ranging from fishes to mammals. The study will utilize zebrafish embryos as they are accessible, transparent, and a powerful genetic model. Migrating FBMNs will be imaged in transparent zebrafish embryos with genetically marked cells, and tracked using light sheet microscopy. The Principal Investigator recently described the pioneer neuron as the first FBMN to migrate on each side of the hindbrain, and demonstrated the critical role of this neuron. Aim 1 will study the newly recognized pioneer neuron by establishing its cellular origins and tracking its subsequent trajectory through development. FBMN tangential migration also relies on interactions with two different pre-laid axon tracts and both interactions depend on adhesion molecule N-Cadherin. Aim 2 will investigate the role of N-Cadherin in mediating interactions between FBMNs and axon tracts, and whether it functions autonomously within neurons during migration. Additional adhesion molecules important for FBMN migration will be identified using RNAseq. An integral part of this project will be the development of new, broadly-applicable computational tools to analyze imaging data.