The long-term goal of this proposal is to understand the molecular mechanisms underlying hair cell development and patterning in the mammalian inner ear. Hair cells are specialized mechno-receptors that are responsible for sensing auditory and vestibular stimuli. Congenital or pathological loss of hair cells in human cochlea causes hearing loss, with a severity that correlates with the extent of missing hair cells. Recent analysis of mice carrying a targeted mutation in the Jagged2 gene, which encodes a cell surface ligand for the Notch family receptors indicates that Notch signaling mediates hair cell differentiation in the mammalian cochlea. Of the four known mouse Notch genes, only Notchl is expressed in the inner ear epithelium that gives rise to both hair cells and supporting cells, suggesting that Notchl may play an essential role in the hair cell development. interestingly, an autosomal dominantly inherited deafness syndrome has been mapped to the same chromosomal region as the human Notchl gene. However, targeted null mutations in the mouse Notchl gene cause early embryonic lethality. To characterize Notchl function in hair cell development, this pilot study examines potential defects in hair cell patterning in the Notchl heterozygous mice. In addition, new gain-of-function and hypomorphic alleles of mouse Notchl will be generated to further characterize the roles of Notch1 in hair cell development. These studies will lead to a better understanding of Notch function in hair cell development and will provide insights to studies of congenital deafness.

Agency
National Institute of Health (NIH)
Institute
National Institute on Deafness and Other Communication Disorders (NIDCD)
Type
Small Research Grants (R03)
Project #
1R03DC004375-01
Application #
6072087
Study Section
Special Emphasis Panel (ZDC1-SRB-S (09))
Program Officer
Johnson, Thomas E
Project Start
2000-01-01
Project End
2002-12-31
Budget Start
2000-01-01
Budget End
2000-12-31
Support Year
1
Fiscal Year
2000
Total Cost
$50,386
Indirect Cost
Name
University of Rochester
Department
Dentistry
Type
Schools of Dentistry
DUNS #
041294109
City
Rochester
State
NY
Country
United States
Zip Code
14627