The overall goals of this research project are to identify the molecular and cellular factors that play a role in the development of the sensory epithelium of the mammalian cochlea (the organ of Corti). The organ of Corti is comprised of at least 6 distinct cell types that are arranged in highly conserved mosaic. The generation of a specific number of each cell type and the arrangement of these cell types into a regular pattern are essential for the normal perception of sound, however our understanding of the factors that play a role in the development of this structure is extremely limited. This project was initiated at the beginning of March, 2000. Therefore at the time of this writing, the project has only been underway for 5 months. In the last 5 months we have identified two genes that may play key roles in the regulation of cellular pattern in the organ of Corti. First, Myt1 a gene that has been shown to play a role in lateral inhibition was found to be expressed in cells that will develop as sensory hair cells. This suggests that Myt1 may play a role in the inhibitory interactions that mediate the formation of an alternating mosaic of hair cells and non-sensory supporting cells. Second we have found that Sox-2, a gene that is required for primary neural induction, is also expressed in the developing cohlear sensory epithelium and may therefore play a similar role in the development of this portion of the auditory system.

Agency
National Institute of Health (NIH)
Institute
National Institute on Deafness and Other Communication Disorders (NIDCD)
Type
Intramural Research (Z01)
Project #
1Z01DC000059-01
Application #
6413267
Study Section
(DIR)
Project Start
Project End
Budget Start
Budget End
Support Year
1
Fiscal Year
2000
Total Cost
Indirect Cost
Name
Deafness & Other Communication Disorders
Department
Type
DUNS #
City
State
Country
United States
Zip Code
Harley, Randall J; Murdy, Joseph P; Wang, Zhirong et al. (2018) Neuronal cell adhesion molecule (NrCAM) is expressed by sensory cells in the cochlea and is necessary for proper cochlear innervation and sensory domain patterning during development. Dev Dyn 247:934-950
Driver, Elizabeth Carroll; Northrop, Amy; Kelley, Matthew W (2017) Cell migration, intercalation and growth regulate mammalian cochlear extension. Development 144:3766-3776
Honda, Keiji; Kim, Sung Huhn; Kelly, Michael C et al. (2017) Molecular architecture underlying fluid absorption by the developing inner ear. Elife 6:
Burns, Joseph C; Kelly, Michael C; Hoa, Michael et al. (2015) Single-cell RNA-Seq resolves cellular complexity in sensory organs from the neonatal inner ear. Nat Commun 6:8557
Coate, Thomas M; Spita, Nathalie A; Zhang, Kaidi D et al. (2015) Neuropilin-2/Semaphorin-3F-mediated repulsion promotes inner hair cell innervation by spiral ganglion neurons. Elife 4:
Kelley, Matthew R; Neath, Ian; Surprenant, Aimee M (2013) Three more semantic serial position functions and a SIMPLE explanation. Mem Cognit 41:600-10
Szarama, Katherine B; Gavara, NĂºria; Petralia, Ronald S et al. (2012) Cytoskeletal changes in actin and microtubules underlie the developing surface mechanical properties of sensory and supporting cells in the mouse cochlea. Development 139:2187-97
Yamamoto, Norio; Okano, Takayuki; Ma, Xuefei et al. (2009) Myosin II regulates extension, growth and patterning in the mammalian cochlear duct. Development 136:1977-86
Driver, Elizabeth Carroll; Pryor, Shannon P; Hill, Patrick et al. (2008) Hedgehog signaling regulates sensory cell formation and auditory function in mice and humans. J Neurosci 28:7350-8
Kelley, Matthew W (2008) Leading Wnt down a PCP path: Cthrc1 acts as a coreceptor in the Wnt-PCP pathway. Dev Cell 15:7-8

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