The long-term goal of the proposed research is to understand the tissue interactions and molecular mechanism underlying induction, patterning and cell fate specification in the vertebrate middle ear. This study examines the tissue interactions and functional mechanisms involved in induction and morphogenesis of the vertebrate middle ear. The ear has multiple components that need to develop and interact correctly for normal hearing. Because the interactions are so complex, there are multiple ways that developmental defects occur through development. As a result of developmental (congenital) defects in a complex system such as the hearing apparatus, hearing loss is one of the most common birth defects (1 in 300-500 newborns affected), with about 10% conductive hearing loss. Middle and outer ear congenital and later anomalies resulting in conductive hearing loss include, microtia, atresia, cholesteatoma, exostoses, otoschlerosis, glomus tumor, myringosclerosis of the tympanic membrane, otitis media and trauma. The morphology of the chick middle ear was described nearly 30 years ago, but few studies of the tissue and molecular interactions required for initiation and patterning of the middle ear using modern molecular methods have been undertaken. Using the chicken embryo, with its numerous advantages as a model organism, crucial studies of both tissue interactions and signaling mechanisms can be accomplished. The chick offers a simple, accessible system in which a single bone, the columella develops, which is essential for sound transmission. Tissue interactions and signaling pathways from other complex mechanisms within the embryo, implicate gene candidates for a role in middle ear development. Signaling pathways have also been implicated by their expression patterns in the right place and at the right time. Gene expression in the chick can be altered by several means and has a high degree of spatial and temporal precision.
We aim 1) to determine the gene expression profile of the columella condensation, replacement and persistent cartilage, and timing of chondrogenesis and ossification of the columella using histology and in situ hybridization analysis, 2) determine if the pharyngeal endoderm, lying adjacent to the site of columella condensation is crucial for induction of the columella condensation by performing tissue manipulation and recombination experiments and 3) manipulate the Fgf and Wnt signaling pathways to determine their role in induction and later development of the columella.

Agency
National Institute of Health (NIH)
Institute
National Institute on Deafness and Other Communication Disorders (NIDCD)
Type
Research Project (R01)
Project #
5R01DC009236-04
Application #
8015212
Study Section
Auditory System Study Section (AUD)
Program Officer
Freeman, Nancy
Project Start
2008-02-05
Project End
2013-01-31
Budget Start
2011-02-01
Budget End
2012-01-31
Support Year
4
Fiscal Year
2011
Total Cost
$281,539
Indirect Cost
Name
Clemson University
Department
Biology
Type
Schools of Earth Sciences/Natur
DUNS #
042629816
City
Clemson
State
SC
Country
United States
Zip Code
29634
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Ray, Poulomi; Hughes, Ami J; Sharif, Misha et al. (2017) Lectins selectively label cartilage condensations and the otic neuroepithelium within the embryonic chicken head. J Anat 230:424-434
Ray, Poulomi; Chapman, Susan C (2015) Cytoskeletal Reorganization Drives Mesenchymal Condensation and Regulates Downstream Molecular Signaling. PLoS One 10:e0134702
Galli, Lisa M; Munji, Roeben N; Chapman, Susan C et al. (2014) Frizzled10 mediates WNT1 and WNT3A signaling in the dorsal spinal cord of the developing chick embryo. Dev Dyn 243:833-843
Freese, Nowlan H; Lam, Brianna A; Staton, Meg et al. (2014) A novel gain-of-function mutation of the proneural IRX1 and IRX2 genes disrupts axis elongation in the Araucana rumpless chicken. PLoS One 9:e112364
Kumar, Megha; Chapman, Susan C (2012) Cloning and expression analysis of Fgf5, 6 and 7 during early chick development. Gene Expr Patterns 12:245-53
Noorai, Rooksana E; Freese, Nowlan H; Wright, Lindsay M et al. (2012) Genome-wide association mapping and identification of candidate genes for the rumpless and ear-tufted traits of the Araucana chicken. PLoS One 7:e40974
Kumar, Megha; Ray, Poulomi; Chapman, Susan C (2012) Fibroblast growth factor and bone morphogenetic protein signaling are required for specifying prechondrogenic identity in neural crest-derived mesenchyme and initiating the chondrogenic program. Dev Dyn 241:1091-103
Chapman, Susan Caroline (2011) Can you hear me now? Understanding vertebrate middle ear development. Front Biosci (Landmark Ed) 16:1675-92
Bleyl, Steven B; Saijoh, Yukio; Bax, Noortje A M et al. (2010) Dysregulation of the PDGFRA gene causes inflow tract anomalies including TAPVR: integrating evidence from human genetics and model organisms. Hum Mol Genet 19:1286-301

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