Abstract

This proposal is formulated to investigate the molecular mechanisms that specify some neural precursor cells to develop as oligodendrocytes, the myelinating cell type of the vertebrate central nervous system. 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.
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 gone 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 describes 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.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
5R01NS046668-05
Application #
7391066
Study Section
Neurogenesis and Cell Fate Study Section (NCF)
Program Officer
Tagle, Danilo A
Project Start
2004-04-01
Project End
2010-01-14
Budget Start
2008-04-01
Budget End
2010-01-14
Support Year
5
Fiscal Year
2008
Total Cost
$264,875
Indirect Cost

  Institution

Name
Vanderbilt University Medical Center
Department
Anatomy/Cell Biology
Type
Schools of Medicine
DUNS #
004413456
City
Nashville
State
TN
Country
United States
Zip Code
37212

  Publications

Ravanelli, Andrew M; Kearns, Christina A; Powers, Rani K et al. (2018) Sequential specification of oligodendrocyte lineage cells by distinct levels of Hedgehog and Notch signaling. Dev Biol 444:93-106
Hughes, Ethan G; Appel, Bruce (2016) The cell biology of CNS myelination. Curr Opin Neurobiol 39:93-100
Hudish, Laura I; Galati, Domenico F; Ravanelli, Andrew M et al. (2016) miR-219 regulates neural progenitors by dampening apical Par protein-dependent Hedgehog signaling. Development 143:2292-304
Hines, Jacob H; Ravanelli, Andrew M; Schwindt, Rani et al. (2015) Neuronal activity biases axon selection for myelination in vivo. Nat Neurosci 18:683-9
Kearns, Christina A; Ravanelli, Andrew M; Cooper, Kirsten et al. (2015) Fbxw7 Limits Myelination by Inhibiting mTOR Signaling. J Neurosci 35:14861-71
Yang, Michele L; Shin, Jimann; Kearns, Christina A et al. (2015) CNS myelination requires cytoplasmic dynein function. Dev Dyn 244:134-45
Ravanelli, Andrew M; Appel, Bruce (2015) Motor neurons and oligodendrocytes arise from distinct cell lineages by progenitor recruitment. Genes Dev 29:2504-15
Mathews, Emily S; Mawdsley, David J; Walker, Macie et al. (2014) Mutation of 3-hydroxy-3-methylglutaryl CoA synthase I reveals requirements for isoprenoid and cholesterol synthesis in oligodendrocyte migration arrest, axon wrapping, and myelin gene expression. J Neurosci 34:3402-12
Hudish, Laura I; Blasky, Alex J; Appel, Bruce (2013) miR-219 regulates neural precursor differentiation by direct inhibition of apical par polarity proteins. Dev Cell 27:387-98
Snyder, Julia L; Kearns, Christina A; Appel, Bruce (2012) Fbxw7 regulates Notch to control specification of neural precursors for oligodendrocyte fate. Neural Dev 7:15

Showing the most recent 10 out of 27 publications