Our lab has identified an interesting relation between members of the Myc and E2f family of cell cycle regulators and chromatin changes and transcriptional regulation of differentiation of oligodendrocyte progenitors. We now propose to use primary cultures and genetic mouse models to test a new mechanistic model of oligodendrocyte differentiation. The results from the proposed experimental plan are likely to advance our knowledge not only in neural development and repair, but also in cancer and nuclear reprogramming and have wide implications for the development of novel therapeutic strategies.

Public Health Relevance

The relationship between cell cycle and differentiation in progenitor cells is critical for a vast number of pathologies, ranging from cancer to repair. Although considerable progress has been made in the study of oncogenes in cellular transformation, still very little is known about their role in physiological conditions. This projet defines the role of Myc and E2F in the oligodendrocyte lineage and proposes a novel model of progenitor differentiation, linking cell cycle exit to chromatin condensation and transcriptional modulation.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
5R01NS052738-09
Application #
8804290
Study Section
Special Emphasis Panel (ZRG1-MDCN-N (02))
Program Officer
Lavaute, Timothy M
Project Start
2007-06-15
Project End
2016-02-29
Budget Start
2015-03-01
Budget End
2016-02-29
Support Year
9
Fiscal Year
2015
Total Cost
$370,781
Indirect Cost
$152,031
Name
Icahn School of Medicine at Mount Sinai
Department
Neurosciences
Type
Schools of Medicine
DUNS #
078861598
City
New York
State
NY
Country
United States
Zip Code
10029
Scaglione, Antonella; Patzig, Julia; Liang, Jialiang et al. (2018) PRMT5-mediated regulation of developmental myelination. Nat Commun 9:2840
McKenzie, Andrew T; Wang, Minghui; Hauberg, Mads E et al. (2018) Brain Cell Type Specific Gene Expression and Co-expression Network Architectures. Sci Rep 8:8868
Moyon, Sarah; Casaccia, Patrizia (2017) DNA methylation in oligodendroglial cells during developmental myelination and in disease. Neurogenesis (Austin) 4:e1270381
Moyon, Sarah; Ma, Dan; Huynh, Jimmy L et al. (2017) Efficient Remyelination Requires DNA Methylation. eNeuro 4:
Liu, Jia; Dupree, Jeffrey L; Gacias, Mar et al. (2016) Clemastine Enhances Myelination in the Prefrontal Cortex and Rescues Behavioral Changes in Socially Isolated Mice. J Neurosci 36:957-62
Liu, Jia; Moyon, Sarah; Hernandez, Marylens et al. (2016) Epigenetic control of oligodendrocyte development: adding new players to old keepers. Curr Opin Neurobiol 39:133-8
Moyon, Sarah; Liang, Jialiang; Casaccia, Patrizia (2016) Epigenetics in NG2 glia cells. Brain Res 1638:183-198
Gacias, Mar; Gaspari, Sevasti; Santos, Patricia-Mae G et al. (2016) Microbiota-driven transcriptional changes in prefrontal cortex override genetic differences in social behavior. Elife 5:
Hernandez, Marylens; Patzig, Julia; Mayoral, Sonia R et al. (2016) Mechanostimulation Promotes Nuclear and Epigenetic Changes in Oligodendrocytes. J Neurosci 36:806-13
Moyon, Sarah; Huynh, Jimmy L; Dutta, Dipankar et al. (2016) Functional Characterization of DNA Methylation in the Oligodendrocyte Lineage. Cell Rep 15:748-760

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