Genetic Analysis of Oligodendrocyte Specification

Vanderbilt University, Nashville TN

Investigators

Linked publications & trials

Abstract

[unreadable] DESCRIPTION (provided by applicant): This proposal is designed to investigate the molecular mechanisms that specify some neural precursor cells to develop as oligodendrocytes, which are critical to vertebrate central nervous system function as they produce the myelin insulation that enables rapid conduction of electrical impulses. Oligodendrocytes are known to arise from a neural precursor cell population that also produces motor neurons. How these precursors decide to make motor neurons or oligodendrocytes is unknown. This work will test the hypothesis that cell-cell signaling mediated by Delta ligands and Notch receptors mediates cell fate decisions that specify oligodendrocytes and will search for additional genes important for oligodendrocyte development. The work takes advantage of transgenic zebrafish that express Green Fluorescent Protein under control of the olig2 promoter, which reveals neural precursors that produce oligodendrocytes and motor neurons in living embryos. Specific Aim 1 is designed to identify all the types of cells that arise from precursors that express olig2 and to determine their lineage relationships, using a combination of transgenic reporter gene expression and in vivo cell labeling. Specific aim 2 tests specific hypotheses concerning the role of Delta-Notch signaling in regulating cell fate decisions among olig2-expressing precursor cells using mutations and transgenic, conditional expression systems. Specific aim 3 involves the use of flow cytometry to purify fluorescent embryonic cells to enable molecular screens intended to identify oligodendrocyte-specific genes. Specific aim 4 entails a genetic screen for mutations that modulate the number of oligodendrocytes in transgenic zebrafish embryos. This work will reveal new information concerning the gene functions that guide neural precursors to develop as oligodendrocytes, which may be utilized for therapies designed to treat diseased and injured nervous systems [unreadable] [unreadable]