CAREER: Genetic factors governing axon-glial development in zebrafish peripheral nerve

Kenyon College, Gambier OH

Investigators

Abstract

Movement and sensation rely on the proper patterning of peripheral nerves, which are made up of long tubular processes (axons) that connect the brain and spinal cord to muscles, sensors and organs in the rest of the body. In animals with backbones (vertebrates), peripheral nerve axons are surrounded by a specialized class of cell, Schwann cells, that physically and chemically interact with the neurons they surround. This study will use zebrafish larvae to better understand the exact ways that Schwann cells interact with neurons and tissues in their surrounding environment (especially muscle) to create properly patterned and functional peripheral nerves. Zebrafish larvae are used because they are transparent and develop peripheral nerves rapidly, enabling the coordinated development of Schwann cells and neurons to be easily studied using a combination of visualization cell movements and gene expression patterns, together with manipulative experiments in normal and mutant animals. All the experiments in this project are incorporated into collegiate coursework and independent projects for undergraduate researchers, providing technical training and education alongside scientific discovery. In addition, undergraduate students will learn best practices in public scientific communication and participate in community-engaged learning by creating new lessons and discovery center exhibits for elementary and high school students. These programs are designed to develop young scientists by improving their technical skills and lessening the communication gap with the public. This study aims to define genetic factors that promote migration and differentiation of myelinating glial cells in peripheral nerves. Neural crest-derived Schwann cells coordinate development along axons to provide the necessary trophic support and insulation to conduct rapid nerve impulses. However, the molecular mechanisms that mediate the interdependent relationship between developing neurons, Schwann cells, and their extracellular environment are not fully defined. To more fully understand these processes, the researchers will take advantage of a novel zebrafish model with muscle patterning defects that disrupt sensory axon guidance and glial migration. This project has three goals: 1) characterize Schwann cell maturation and axon elongation in wild-type and mutant zebrafish larvae, 2) test the hypothesis that a basic helix-loop-helix transcription factor functions in body wall muscle to non-cell-autonomously regulate axon elongation and glial migration, and 3) identify muscle-derived guidance cues that are necessary and sufficient for glial cell migration and differentiation using in vivo gene expression analysis and in vitro culture studies. Thus, this study will uncover key molecules that function specifically at the nexus of neural, glial, and muscle development in vertebrates. This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.