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 #
5R01NS052738-07
Application #
8427335
Study Section
Special Emphasis Panel (ZRG1-MDCN-N (02))
Program Officer
Owens, David F
Project Start
2007-06-15
Project End
2016-02-29
Budget Start
2013-03-01
Budget End
2014-02-28
Support Year
7
Fiscal Year
2013
Total Cost
$357,804
Indirect Cost
$146,710
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
Magri, Laura; Swiss, Victoria A; Jablonska, Beata et al. (2014) E2F1 coregulates cell cycle genes and chromatin components during the transition of oligodendrocyte progenitors from proliferation to differentiation. J Neurosci 34:1481-93
Magri, L; Gacias, M; Wu, M et al. (2014) c-Myc-dependent transcriptional regulation of cell cycle and nucleosomal histones during oligodendrocyte differentiation. Neuroscience 276:72-86
Gacias, Mar; Gerona-Navarro, Guillermo; Plotnikov, Alexander N et al. (2014) Selective chemical modulation of gene transcription favors oligodendrocyte lineage progression. Chem Biol 21:841-54
Dutta, Dipankar J; Zameer, Andleeb; Mariani, John N et al. (2014) Combinatorial actions of Tgf? and Activin ligands promote oligodendrocyte development and CNS myelination. Development 141:2414-28
Huynh, Jimmy L; Garg, Paras; Thin, Tin Htwe et al. (2014) Epigenome-wide differences in pathology-free regions of multiple sclerosis-affected brains. Nat Neurosci 17:121-30
Gacias, Mar; Casaccia, Patrizia (2013) Promoting return of function in multiple sclerosis: An integrated approach. Mult Scler Relat Disord 2:
Huynh, Jimmy L; Casaccia, Patrizia (2013) Epigenetic mechanisms in multiple sclerosis: implications for pathogenesis and treatment. Lancet Neurol 12:195-206
Gil-Perotin, Sara; Haines, Jeffery D; Kaur, Jasbir et al. (2011) Roles of p53 and p27(Kip1) in the regulation of neurogenesis in the murine adult subventricular zone. Eur J Neurosci 34:1040-52
Liu, Jia; Casaccia, Patrizia (2010) Epigenetic regulation of oligodendrocyte identity. Trends Neurosci 33:193-201
Yu, Yang; Casaccia, Patrizia; Lu, Q Richard (2010) Shaping the oligodendrocyte identity by epigenetic control. Epigenetics 5:124-8

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