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Manzoor A. Bhat, M.S., Ph.D.

Vice Dean for Research

Long School of Medicine

Professor, Cellular and Integrative Physiology

Currently seeking M.S. & Ph.D. students

Intricate molecular interactions between neurons and glial cells form the underlying basis of axonal insulation across species. Mutations in human genes that affect insulation of axons are associated with profound disturbances in normal impulse conduction and significant neurological disabilities. We are investigating the genetic and molecular basis of complex and reciprocal interactions between various types of glial cells, which play a key role in axonal insulation, blood-brain barrier formation and axon guidance across species. In vertebrates axonal insulation is achieved by myelination carried out by glial cells (Schwann cells and oligodendrocytes). The myelinated nerve fibers are organized into distinct domains that are necessary for rapid saltatory conduction. These domains include the nodes of Ranvier and the flanking paranodal regions where myelin loops closely appose and form axo-glial septate junctions. We identified the vertebrate homologs of the Drosophila septate junction proteins and demonstrated a conserved role for these proteins in the organization and function of the axo-glial septate junctions in myelinated axons. 

We generated Caspr, and Neurofascin (homologs of Drosophila nrx IV and nrg, respectively) mutant mice and demonstrated that in these mutants, paranodal axo-glial septate junctions fail to form and the axonal domain organization is disrupted. These defects result in severe motor deficits, decrease in nerve conduction velocity and axonal degeneration, thus demonstrating a critical role for these proteins in axon-glial interactions in myelinated axons. Our recent studies in mice, using neuron- and myelinating glia-specific inducible-Cre lines, show that axo-glial junction disruption in adults results in slow but progressive neurological disabilities leading to paralysis. These adult mouse mutants serve as models for human myelin-related pathologies.

 

For more details about our lab, please visit www.bhatlab.org