Abstract

The early development of the inner ear occurs in three phases: formation of the otic placode; morphogenesis of the otic placode to form the otocyst; and regional patterning of the otocyst. Each phase is characterized by inductive interactions among different tissues. Although several signaling systems have been implicated in the control of the phases, the FGF signaling system clearly plays a critical role and is a focus of this proposal. This project combines the broad technical and scientific expertise of two investigators and use two animal models to examine the cellular, molecular and genetic control of early inner ear development.
In aim 1, three sets of experiments will be conducted on the early rudiments of the inner ear to elucidate the cellular plays involved in their development, and the interactions that are required as well as sufficient for their induction, morphogenesis and early patterning.
In aim 2, three sets of experiments will be conducted to characterize the roles of FGF signaling in these central events of inner ear development. Collectively, these studies will provide important new information on the normal development of the inner ear and the cellular and molecular factors that regulate this process. Additionally, the results will furnish insight into mechanisms by which development goes awry, causing serious birth defects of the auditory system in humans.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute on Deafness and Other Communication Disorders (NIDCD)
Type
Research Project (R01)
Project #
5R01DC004185-04
Application #
6634501
Study Section
Special Emphasis Panel (ZRG1-IFCN-6 (01))
Program Officer
Freeman, Nancy
Project Start
2000-05-01
Project End
2005-04-30
Budget Start
2003-05-01
Budget End
2004-04-30
Support Year
4
Fiscal Year
2003
Total Cost
$352,500
Indirect Cost

  Institution

Name
University of Utah
Department
Biology
Type
Schools of Medicine
DUNS #
009095365
City
Salt Lake City
State
UT
Country
United States
Zip Code
84112

  Publications

Jackson, Abigail; Kasah, Sahrunizam; Mansour, Suzanne L et al. (2014) Endoderm-specific deletion of Tbx1 reveals an FGF-independent role for Tbx1 in pharyngeal apparatus morphogenesis. Dev Dyn 243:1143-51
Urness, Lisa D; Bleyl, Steven B; Wright, Tracy J et al. (2011) Redundant and dosage sensitive requirements for Fgf3 and Fgf10 in cardiovascular development. Dev Biol 356:383-97
Nishita, Junko; Ohta, Sho; Bleyl, Steven B et al. (2011) Detection of isoform-specific fibroblast growth factor receptors by whole-mount in situ hybridization in early chick embryos. Dev Dyn 240:1537-47
Ohta, Sho; Mansour, Suzanne L; Schoenwolf, Gary C (2010) BMP/SMAD signaling regulates the cell behaviors that drive the initial dorsal-specific regional morphogenesis of the otocyst. Dev Biol 347:369-81
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
Paxton, Christian N; Bleyl, Steven B; Chapman, Susan C et al. (2010) Identification of differentially expressed genes in early inner ear development. Gene Expr Patterns 10:31-43
Urness, Lisa D; Paxton, Christian N; Wang, Xiaofen et al. (2010) FGF signaling regulates otic placode induction and refinement by controlling both ectodermal target genes and hindbrain Wnt8a. Dev Biol 340:595-604
Hatch, Ekaterina P; Urness, Lisa D; Mansour, Suzanne L (2009) Fgf16(IRESCre) mice: a tool to inactivate genes expressed in inner ear cristae and spiral prominence epithelium. Dev Dyn 238:358-66
Abler, Lisa L; Mansour, Suzanne L; Sun, Xin (2009) Conditional gene inactivation reveals roles for Fgf10 and Fgfr2 in establishing a normal pattern of epithelial branching in the mouse lung. Dev Dyn 238:1999-2013
Hatch, Ekaterina P; Noyes, C Albert; Wang, Xiaofen et al. (2007) Fgf3 is required for dorsal patterning and morphogenesis of the inner ear epithelium. Development 134:3615-25

Showing the most recent 10 out of 33 publications