Our major accomplishments this year are in the following areas: 1) Role of hindbrain in inner ear development Using tissue extirpation and translocation techniques in chicken embryos, we show that the hindbrain confers the dorsoventral but not anteroposterior axial information to the developing inner ear. Sonic hedgehog emanated from either the floor plate or the notochord is a major factor in dictating ventral patterning of the inner ear. Furthermore, normal dorsal otic tissues will acquire ventral fates when juxtaposed to ventral hindbrain tissues in ovo, over riding any potential dorsalizing signals from other tissues. These results suggest that hindbrain is the major tissue responsible for dictating the dorsal-ventral axis of the inner ear. 2) Role of Gbx2 in inner ear development Gbx2 is a homeobox-containing transcription factor. The absence of Gbx2 function in mice results in inner ear defects that involve both vestibular and auditory components. These inner ear phenotypes are remarkably similar to those reported in kreisler mice, which have inner ear defects attributed to defects in the hindbrain. Our gene expression analyses suggest that activation of Gbx2 expression in inner ear is an important step downstream of hindbrain signaling.

Agency
National Institute of Health (NIH)
Institute
National Institute on Deafness and Other Communication Disorders (NIDCD)
Type
Intramural Research (Z01)
Project #
1Z01DC000021-12
Application #
7130159
Study Section
(LMB)
Project Start
Project End
Budget Start
Budget End
Support Year
12
Fiscal Year
2005
Total Cost
Indirect Cost
Name
Deafness & Other Communication Disorders
Department
Type
DUNS #
City
State
Country
United States
Zip Code
Chang, Weise; Lin, Zhengshi; Kulessa, Holger et al. (2008) Bmp4 is essential for the formation of the vestibular apparatus that detects angular head movements. PLoS Genet 4:e1000050
Hwang, Chan-Ho; Wu, Doris K (2008) Noggin heterozygous mice: an animal model for congenital conductive hearing loss in humans. Hum Mol Genet 17:844-53
Bok, Jinwoong; Chang, Weise; Wu, Doris K (2007) Patterning and morphogenesis of the vertebrate inner ear. Int J Dev Biol 51:521-33
Bok, Jinwoong; Brunet, Lisa J; Howard, Omar et al. (2007) Role of hindbrain in inner ear morphogenesis: analysis of Noggin knockout mice. Dev Biol 311:69-78
Bok, Jinwoong; Dolson, Diane K; Hill, Patrick et al. (2007) Opposing gradients of Gli repressor and activators mediate Shh signaling along the dorsoventral axis of the inner ear. Development 134:1713-22
Bok, Jinwoong; Bronner-Fraser, Marianne; Wu, Doris K (2005) Role of the hindbrain in dorsoventral but not anteroposterior axial specification of the inner ear. Development 132:2115-24
Lin, Zhengshi; Cantos, Raquel; Patente, Maria et al. (2005) Gbx2 is required for the morphogenesis of the mouse inner ear: a downstream candidate of hindbrain signaling. Development 132:2309-18
Walker, Diana L; Vacha, Scott J; Kirby, Margaret L et al. (2005) Connexin43 deficiency causes dysregulation of coronary vasculogenesis. Dev Biol 284:479-98
Burton, Quianna; Cole, Laura K; Mulheisen, Michael et al. (2004) The role of Pax2 in mouse inner ear development. Dev Biol 272:161-75
Chang, Weise; Brigande, John V; Fekete, Donna M et al. (2004) The development of semicircular canals in the inner ear: role of FGFs in sensory cristae. Development 131:4201-11

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