Genetic and cellular analysis of glial development and function in vertebrates

NIH Pandemic-Era Grants

Pandemic Era Grants

2024

Document text

Principal Investigator: WILLIAM S TALBOT
Organization: STANFORD UNIVERSITY
Fiscal Year: 2024
Award: $531,319
Funding agency: National Institute of Neurological Disorders and Stroke

Glia are non-neuronal cells with diverse functions that range from forming the myelin sheath to defending the
brain against infection. A major goal of our research is to use the powerful experimental advantages of
zebrafish to discover new genes that are essential for the development and function of two classes of glia in
the CNS, oligodendrocytes and microglia.
Oligodendrocytes form myelin on axons in the CNS. After an oligodendrocyte begins to myelinate axons, it has
only a short developmental window (or “critical period”) to extend new myelinating processes. Using genetic
and cellular approaches in zebrafish, we have identified a number of positive and negative regulators of
myelination. One of our goals is to determine how these factors control myelination during development,
neural plasticity, and remyelination. In addition, we will investigate the molecular basis of the critical period.
Microglia are highly motile, phagocytic glial cells in the CNS that destroy pathogens and clear debris such as
apoptotic cells and damaged axons. Despite the importance of microglia in CNS health and disease, many
critical questions remain to be addressed about these cells. We have conducted zebrafish mutational screens
to discover essential microglial genes, and we are characterizing their functions using in vivo imaging and
other approaches.
The mechanistic insight gained from these studies will advance our fundamental understanding of the central
nervous system, illuminate the pathways that are disrupted in diseases of the brain, and suggest avenues
toward therapies for neurological disorders.

Terms: <Address><Apoptotic><Axon><Biologic Models><Biological Models><Brachydanio rerio><Brain><Brain Diseases><Brain Disorders><Brain Nervous System><CNS Nervous System><CNS plasticity><Cell Body><Cell Function><Cell Physiology><Cell Process><Cells><Cellular Function><Cellular Physiology><Cellular Process><Central Nervous System><Danio rerio><Development><Disease><Disorder><Encephalon><Encephalon Diseases><Genes><Genetic><Glia><Glial Cells><Goals><Health><Hortega cell><Infection><Intracranial CNS Disorders><Intracranial Central Nervous System Disorders><Kolliker's reticulum><Microglia><Model System><Molecular><Motility><Myelin><Myelin Sheath><Nervous System Diseases><Nervous System Disorder><Neuraxis><Neuroglia><Neuroglial Cells><Neurologic Disorders><Neurological Disorders><Neuronal Plasticity><Non-neuronal cell><Nonneuronal cell><Oligodendrocytes><Oligodendrocytus><Oligodendroglia><Oligodendroglia Cell><Pathway interactions><Phagocytes><Phagocytic Cell><Process><Research><Role><Subcellular Process><Vertebrate Animals><Vertebrates><Zebra Danio><Zebra Fish><Zebrafish><amebocyte><axon damage><axon injury><axonal damage><axonal injury><central nervous system plasticity><critical period><developmental><gitter cell><glial cell development><glial development><imaging in vivo><in vivo imaging><insight><mesoglia><microglial cell><microgliocyte><mutation scanning><mutation screening><myelination><nerve cement><neural plasticity><neurological disease><neuroplastic><neuroplasticity><pathogen><pathway><perivascular glial cell><re-myelinate><re-myelination><remyelinate><remyelination><social role><vertebrata>