The research addresses fundamental processes in the formation and survival of neurons, the impulse-conducting cells of the brain and nervous system. One goal is to determine how the decision of stem or precursor cells to become neurons through expression of proneural Class II bHLH genes relies on the earlier expression of genes that create a molecular environment either facilitating or antagonizing the future function of proneural Class II bHLH genes. Genetic and developmental studies of the fruitfly retina and the development of its photoreceptor neurons will be performed to delineate the regulatory network affecting proneural Class II bHLH genes. Molecular genetic studies will identify the specific DNA sequences that are responsible for gene expression and which therefore influence where and when neuronal photoreceptor cells are formed during eye development. A further goal is to determine how the genes that regulate neuronal determination also affect growth and the cell cycle. Genetic and molecular approaches will be taken to elucidate these connections between neurogenesis, growth, and cell cycle arrest, and which are perturbed in cancers and neurodegenerative diseases.

Public Health Relevance

Neuronal deficits underlie common, serious health issues including retinitis pigmentosa, macular degeneration, stroke, Alzheimer's disease, Parkinson's Disease, Huntington's disease, and Amyotrophic Lateral Sclerosis. Replacing or limiting neuronal loss in these conditions would significantly improve or reverse symptoms. Our studies will suggest new approaches to neuroprotection and regenerative approaches involving proliferation and specification of replacement neurons.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
5R01GM047892-20
Application #
8237004
Study Section
Biology and Diseases of the Posterior Eye Study Section (BDPE)
Program Officer
Hoodbhoy, Tanya
Project Start
1992-08-01
Project End
2014-03-31
Budget Start
2012-04-01
Budget End
2013-03-31
Support Year
20
Fiscal Year
2012
Total Cost
$402,633
Indirect Cost
$160,083
Name
Albert Einstein College of Medicine
Department
Genetics
Type
Schools of Medicine
DUNS #
110521739
City
Bronx
State
NY
Country
United States
Zip Code
10461
Baker, Nicholas E; Li, Ke; Quiquand, Manon et al. (2014) Eye development. Methods 68:252-9
Baker, Nicholas E (2013) Developmental regulation of nucleolus size during Drosophila eye differentiation. PLoS One 8:e58266
Bhattacharya, Abhishek; Baker, Nicholas E (2011) A network of broadly expressed HLH genes regulates tissue-specific cell fates. Cell 147:881-92
Baker, Nicholas E; Firth, Lucy C (2011) Retinal determination genes function along with cell-cell signals to regulate Drosophila eye development: examples of multi-layered regulation by master regulators. Bioessays 33:538-46
Lubensky, David K; Pennington, Matthew W; Shraiman, Boris I et al. (2011) A dynamical model of ommatidial crystal formation. Proc Natl Acad Sci U S A 108:11145-50
Firth, Lucy C; Bhattacharya, Abhishek; Baker, Nicholas E (2010) Cell cycle arrest by a gradient of Dpp signaling during Drosophila eye development. BMC Dev Biol 10:28
Bhattacharya, Abhishek; Baker, Nicholas E (2009) The HLH protein Extramacrochaetae is required for R7 cell and cone cell fates in the Drosophila eye. Dev Biol 327:288-300
Baker, Nicholas E; Bhattacharya, Abhishek; Firth, Lucy C (2009) Regulation of Hh signal transduction as Drosophila eye differentiation progresses. Dev Biol 335:356-66
Firth, Lucy C; Baker, Nicholas E (2009) Retinal determination genes as targets and possible effectors of extracellular signals. Dev Biol 327:366-75
Firth, Lucy C; Baker, Nicholas E (2007) Spitz from the retina regulates genes transcribed in the second mitotic wave, peripodial epithelium, glia and plasmatocytes of the Drosophila eye imaginal disc. Dev Biol 307:521-38

Showing the most recent 10 out of 27 publications