Neuronal cell types are the building blocks of brain function and differences between cell types are critical to understanding nervous system disease. New genetic and genomic resources are increasingly available for identifying and manipulating specific cell types in the mouse. We will create a unified gateway to these reagents and a platform for integrating and sharing data obtained with them to enhance progress on the difficult problem of identifying the neuronal cell types of the mammalian brain. We will implement a searchable, freely shared open source database of resources and experimental results. We will annotate the anatomical location of targeted cell types within each of ~90 existing driver/reporter strains by aligning individual sections to the Allen Brain Reference Atlas and will develop new strains using a novel lentiviral enhancer trap strategy in mice. For a subset of cell types we will perform genome-gene expression profiling to enhance insights from this unbiased metric of relationships between neuronal cell types. We will integrate the cell type database and improved atlas viewer with tools for viewing cell type-specific morphology, physiology and gene expression data, and will link these data with other available brain atlas and genomic databases. The ability to freely search and compare cell-type specific phenotypes and gene expression data will enable members of the scientific community to develop specific hypotheses about the molecular bases of specific cellular phenotypes and to improve schemes for classifying neuronal cell types.

Public Health Relevance

Neuronal cell types are the functional building blocks of the brain. We will create a Database of Mammalian Neuronal Cell-types. To enhance the usefulness of this effort we will generate new strains of mice that allow genetic targeting of specific cell types and will profile the gene expression patterns that make cell types different from one another. The great majority of brain diseases are diseases that primarily affect specific cell types, and therefore integrating and improving our understanding of cell types in the mammalian brain may help study of these diseases.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
5R01NS075007-02
Application #
8413045
Study Section
Special Emphasis Panel (ZRG1-NT-L (09))
Program Officer
Riddle, Robert D
Project Start
2012-02-01
Project End
2017-01-31
Budget Start
2013-02-01
Budget End
2014-01-31
Support Year
2
Fiscal Year
2013
Total Cost
$340,476
Indirect Cost
$129,383
Name
Brandeis University
Department
Biology
Type
Schools of Arts and Sciences
DUNS #
616845814
City
Waltham
State
MA
Country
United States
Zip Code
02454
Grange, Pascal; Bohland, Jason W; Okaty, Benjamin W et al. (2014) Cell-type-based model explaining coexpression patterns of genes in the brain. Proc Natl Acad Sci U S A 111:5397-402
Sugino, Ken; Hempel, Chris M; Okaty, Benjamin W et al. (2014) Cell-type-specific repression by methyl-CpG-binding protein 2 is biased toward long genes. J Neurosci 34:12877-83