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; Brown, Nadean L (2018) All in the family: proneural bHLH genes and neuronal diversity. Development 145:
Li, Ke; Baker, Nicholas E (2018) Regulation of the Drosophila ID protein Extra macrochaetae by proneural dimerization partners. Elife 7:
Wang, Lan-Hsin; Baker, Nicholas E (2018) Spatial regulation of expanded transcription in the Drosophila wing imaginal disc. PLoS One 13:e0201317
Baker, Nicholas E (2017) Patterning the eye: A role for the cell cycle? Dev Biol 430:263-265
Bhattacharya, Abhishek; Li, Ke; Quiquand, Manon et al. (2017) The Notch pathway regulates the Second Mitotic Wave cell cycle independently of bHLH proteins. Dev Biol 431:309-320
Wang, Lan-Hsin; Baker, Nicholas E (2015) Salvador-Warts-Hippo pathway in a developmental checkpoint monitoring helix-loop-helix proteins. Dev Cell 32:191-202
Wang, Lan-Hsin; Baker, Nicholas E (2015) E Proteins and ID Proteins: Helix-Loop-Helix Partners in Development and Disease. Dev Cell 35:269-80
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 (2012) The role of the bHLH protein hairy in morphogenetic furrow progression in the developing Drosophila eye. PLoS One 7:e47503

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