Developmental Regulation of Axon Pathway Formation

Ohio State University Research Foundation -Do Not Use, Columbus OH

Investigators

Abstract

Beattie Lay Summary Movement is controlled by connections established during development between motor neurons and muscle cells. Motor neurons extend processes called axons out from their cell bodies, which leave the spinal cord and extend through the developing embryo to contact the appropriate muscle fibers. This process, referred to as axon guidance, is a fundamental component of development and is essential for survival. Axon guidance is highly precise with growth cones, the growing tip of axons, making few navigational errors as they extend along stereotyped routes or pathways. While numerous examples of axon guidance events in vertebrates have been described at the cellular level, less is known about the molecules that control these events. The goal of this research is to elucidate the molecules and mechanisms that control motor axon guidance in vertebrates. To this end, the experiments outlined in this proposal focus on mutations that disrupt motor axon guidance in the embryonic zebrafish. Zebrafish is an excellent model system for studying vertebrate motor axon guidance due to its relatively simple nervous system, the ability to study embryos at early stages of development, and the capability to induce, recover, and clone mutations. The mutation stumpy dramatically and specifically affects the ability of motor axons to reach their target muscles. Instead of progressing along their pathways, motor axons in stumpy mutants stop at intermediate targets; places along the pathway where growth cones normally pause, branch, or turn. Stumpy functions to enable growth cones to proceed past intermediate targets and to reach their target muscle fibers. A series of genetic, cellular, and molecular approaches will elucidate what kind of molecule stumpy is and how it is functioning. Moreover, another mutation has been identified that interacts with stumpy at the genetic level indicating that these genes work together to promote normal motor axon guidance. Studying these mutations will provide novel insights into the genetic control of vertebrate motor axon guidance and will identify molecules that function in this essential developmental process.