Molecular mechanisms underlying motor exit point glia function

The National Institute of Neurological Disorders and Stroke awarded Florida Atlantic University $448,664 on September 1, 2026, under the Extramural Research Programs in the Neurosciences and Neurological Disorders program (CFDA 93.853) to investigate molecular mechanisms underlying motor exit point glia function.

The funded research characterizes a novel population of glia residing at transition zones between the central and peripheral nervous systems. Motor exit point glia originate in the spinal cord, migrate into the peripheral nervous system to myelinate motor axons, and regulate oligodendrocyte migration at the spinal cord's ventral border. The project pursues three specific aims: defining motor exit point glia gene expression profiles using single-cell RNA-sequencing datasets and in situ hybridization to validate markers and generate reporter and mutant lines; investigating peripheral nervous system myelination by motor exit point glia; and characterizing regulatory mechanisms that govern the migration and function of these hybrid central/peripheral glial cells. The work will generate hypothesis-driven projects for incoming students.

Performance occurs at Florida Atlantic University in Boca Raton, Florida, over the period of September 1, 2026, through August 31, 2029.

Abstract

The nervous system is divided into two separate, yet connected, domains: the central nervous system (CNS) and peripheral nervous system (PNS), in which distinct cell types often carry out the same biological function. For instance, oligodendrocytes are restricted to the CNS and schwann cells to the PNS, and both glial cell types function to myelinate axons, facilitating efficient nerve conduction. The rationale for this project is that the nervous system boundaries, called transition zones (TZ), that were long thought to be selectively permeable to axons only, are occupied by dynamic glial cells and their permeability is precisely regulated over the course of nervous system development. We recently characterized a novel population of glia that reside at these TZS. Motor exit point (MEP) glia originate in the spinal cord and migrate into the PNS to myelinate motor axons. MEP glia also regulate oligodendrocyte migration at the ventral border of the spinal cord and prevent oligodendrocytes to ectopically migrate into the PNS. Unlike traditional myelinating glia, MEP glia display central/peripheral hybrid characteristics, and are conveniently located at the edge of the spinal cord, in close proximity to the CNS and PNS. The central hypothesis, which is formulated based on preliminary data, is that these two subtypes of CNS- derived glia can function in both halves of the nervous system. The objective of this project will be accomplished by three specific aims: (1) define MEP glia gene expression profile. Using single cell RNA-sequencing zebrafish datasets, we will use in situ hybridization to uncover additional MEP glial markers. For each validated marker, we will create reporter and mutant lines, and study the function of genes previously unknown in the context of glial biology. This aim will generate hypothesis-driven projects for incoming students. (2) investigate PNS myelinating glia migrating into the spinal cord. In a recent study, we genetically induced the presence of schwann cells and MEP glia in the post-embryonic spinal cord. In this aim, we will determine their ability to produce myelin in the healthy and demyelinated CNS. (3) characterize oligodendrocyte myelin in the PNS. The working hypothesis is that at the CNS/PNS interface, motor axon myelination involves multiple populations of myelinating glia, and this architecture is plastic upon perturbations. We previously demonstrated the presence of myelinating oligodendrocytes on PNS motor axons upon perturbation, but the integrity and maintenance of these ectopic myelin sheaths remain unknown. This project is innovative because we propose to investigate a previously unknown source of myelin-forming cells and their plasticity. The knowledge we will gain from the proposed experiments may provide an innovative basis for novel myelin-repair therapies.