This proposal seeks to elucidate mechanisms of early development of the inner ear in the zebrafish, Danio redo. The inner ear arises from a simple thickening on the surface of the embryo termed the otic placode. Our recent studies have revealed mechanisms underlying induction of the otic placode, early patterning of the otic placode, and specification of sensory hair ceils. We will follow up on these studies. Induction and early patterning of the otic placode requires Fgf signaling, and it has been suggested that another factor, Wnt8, participates in this process. Using mis-expression and loss of function techniques, we will test the relative roles of Fgf3, Fgf8, Wnt8, and Wnt8b in these processes. We will also examine the role of Fgf signaling in subsequent differentiation of sensory hair cells. The earliest known markers of otic development are members of the Pax2/5/8 family of transcription factors, which we hypothesize help mediate induction by Fgf signaling. The epistatic relationships between pax and fgf functions will be examined. Finally, we will identify additional genes acting in these pathways by screening for second site mutations that enhance the ear defects caused by mutations in pax and fgf genes. These early developmental processes, and the genetic pathways controlling them, are highly conserved. Indeed, disruption of these processes can lead to deafness in humans. Therefore, achieving a fuller understanding of how the inner ear develops could eventually lead to effective medical interventions for human deafness or other disorders of the inner ear.

Agency
National Institute of Health (NIH)
Institute
National Institute on Deafness and Other Communication Disorders (NIDCD)
Type
Research Project (R01)
Project #
5R01DC003806-09
Application #
7009896
Study Section
Special Emphasis Panel (ZRG1-IFCN-6 (01))
Program Officer
Freeman, Nancy
Project Start
2003-05-01
Project End
2008-02-28
Budget Start
2006-03-01
Budget End
2007-02-28
Support Year
9
Fiscal Year
2006
Total Cost
$316,626
Indirect Cost
Name
Texas A&M University
Department
Biology
Type
Schools of Arts and Sciences
DUNS #
078592789
City
College Station
State
TX
Country
United States
Zip Code
77845
Gou, Yunzi; Vemaraju, Shruti; Sweet, Elly M et al. (2018) sox2 and sox3 Play unique roles in development of hair cells and neurons in the zebrafish inner ear. Dev Biol 435:73-83
Gou, Yunzi; Guo, Jinbai; Maulding, Kirstin et al. (2018) sox2 and sox3 cooperate to regulate otic/epibranchial placode induction in zebrafish. Dev Biol 435:84-95
Kantarci, Husniye; Gerberding, Andrea; Riley, Bruce B (2016) Spemann organizer gene Goosecoid promotes delamination of neuroblasts from the otic vesicle. Proc Natl Acad Sci U S A 113:E6840-E6848
Kantarci, Husniye; Edlund, Renee K; Groves, Andrew K et al. (2015) Tfap2a promotes specification and maturation of neurons in the inner ear through modulation of Bmp, Fgf and notch signaling. PLoS Genet 11:e1005037
Edlund, Renée K; Ohyama, Takahiro; Kantarci, Husniye et al. (2014) Foxi transcription factors promote pharyngeal arch development by regulating formation of FGF signaling centers. Dev Biol 390:1-13
Maulding, Kirstin; Padanad, Mahesh S; Dong, Jennifer et al. (2014) Mesodermal Fgf10b cooperates with other fibroblast growth factors during induction of otic and epibranchial placodes in zebrafish. Dev Dyn 243:1275-85
Bhat, Neha; Kwon, Hye-Joo; Riley, Bruce B (2013) A gene network that coordinates preplacodal competence and neural crest specification in zebrafish. Dev Biol 373:107-17
Vemaraju, Shruti; Kantarci, Husniye; Padanad, Mahesh S et al. (2012) A spatial and temporal gradient of Fgf differentially regulates distinct stages of neural development in the zebrafish inner ear. PLoS Genet 8:e1003068
Padanad, Mahesh S; Bhat, Neha; Guo, Biwei et al. (2012) Conditions that influence the response to Fgf during otic placode induction. Dev Biol 364:1-10
Sweet, Elly M; Vemaraju, Shruti; Riley, Bruce B (2011) Sox2 and Fgf interact with Atoh1 to promote sensory competence throughout the zebrafish inner ear. Dev Biol 358:113-21

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