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Genetic Analysis of Inner Ear Development in Zebrafish

Award Number: R01DC003806
ORGANIZATION: NATIONAL INSTITUTE ON DEAFNESS AND OTHER COMMUNICATION DISORDERS
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 05/01/1998
PERIOD OF PERFORMANCE END DATE: 03/31/2024

Group Awards By:

View Award Description

Genetic Analysis of Inner Ear Development in Zebrafish - Project Summary Using zebrafish as a model organism, experiments will explore mechanisms by which mechonsensory hair cells and neurons of the inner ear are formed and maintained. Fgf and Wnt signaling pathways cooperate to establish hair cells, and at the same time Fgf and Wnt work in opposition during formation of neurons. How Fgf and Wnt are coordinated to regulate these diverse responses is poorly understood. This will be investigated in three specific aims. 1) Study how transcription factors Pax2, Pax5, Sp5a, and Sp5l mediate discrete aspects of Fgf and Wnt signaling. Experiments will examine how mutations in these genes alter the response to Fgf and Wnt. In addition to evaluating loss-of-function mutations, transgenic lines will be used to overexpress these factors. 2) Explore how Pax2 and Pax5 promote hair cell survival. In embryos lacking Pax2 or Pax5, hair cells initially form but are later extruded from the developing inner ear. Experiments will test the idea that Pax2 and Pax5 are required to maintain cell adhesion molecules that normally hold hair cells in place. This will be tested by treating embryos with drugs that stabilize adhesion complexes, and by using transgenic lines to overexpress cell adhesion molecules to see whether hair cell loss is prevented. 3) Previous studies uncovered a completely novel mechanism by which cells in the developing ear undergo a change in metabolism similar to the “Warburg Effect” seen in metastatic tumors. Specifically, ear cells upregulate glycolysis and fermentation (despite abundant oxygen) in order to produce and secrete high levels of lactate. Disruption of lactate production impairs production of hair cells and neurons, in part by weakening the response to Fgf. Proposed experiments will further explore how lactate impacts Fgf signaling, and also test whether lactate affects Wnt signaling. In addition, the function of Foxm1, a transcription factor often responsible for activating the Warburg Effect in tumors, will be tested in the context of inner ear development. Foxm1 also mediates Wnt and Fgf in tumors, hence the effects of mutations in Foxm1 or misexpressing Foxm1 on Fgf and Wnt signaling will be tested. Together, these studies will provide fundamental insights into mechanisms of hair cell and neural development. Because developmental mechanisms are broadly conserved, studying how these genes work in zebrafish could suggest candidates for “gene therapy” to restore hearing in mammals.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2026 ( Subtotal = -$39 )
2026	2023	TEXAS A & M UNIVERSITY	400 HARVEY MITCHELL PKY S STE 300	COLLEGE STATION	TX	77845	BRAZOS	USA	Research Related to Deafness and Communication Disorders	000	25	2/11/2026	NON-COMPETING CONTINUATION	-$39
														Subtotal = -$39

Issue Date FY: 2025 ( Subtotal = -$13 )
2025	2023	TEXAS A & M UNIVERSITY	400 HARVEY MITCHELL PKY S STE 300	COLLEGE STATION	TX	77845	BRAZOS	USA	Research Related to Deafness and Communication Disorders	000	25	6/30/2025	NON-COMPETING CONTINUATION	-$13
														Subtotal = -$13

Issue Date FY: 2023 ( Subtotal = $459,469 )
2023	2023	TEXAS A & M UNIVERSITY	400 HARVEY MITCHELL PKY S STE 300	COLLEGE STATION	TX	77845	BRAZOS	USA	Research Related to Deafness and Communication Disorders	000	25	3/15/2023	NON-COMPETING CONTINUATION	$459,469
														Subtotal = $459,469

Issue Date FY: 2022 ( Subtotal = $459,469 )
2022	2022	TEXAS A & M UNIVERSITY	400 HARVEY MITCHELL PKY S STE 300	COLLEGE STATION	TX	77845	BRAZOS	USA	Research Related to Deafness and Communication Disorders	000	24	4/20/2022	NON-COMPETING CONTINUATION	$459,469
														Subtotal = $459,469

Issue Date FY: 2021 ( Subtotal = $459,469 )
2021	2021	TEXAS A & M UNIVERSITY	400 HARVEY MITCHELL PKY S STE 300	COLLEGE STATION	TX	77845	BRAZOS	USA	Research Related to Deafness and Communication Disorders	000	23	3/16/2021	NON-COMPETING CONTINUATION	$459,469
														Subtotal = $459,469

Issue Date FY: 2020 ( Subtotal = $459,470 )
2020	2020	TEXAS A & M UNIVERSITY	400 HARVEY MITCHELL PKY S STE 300	COLLEGE STATION	TX	77845	BRAZOS	USA	Research Related to Deafness and Communication Disorders	001	22	3/18/2020	NON-COMPETING CONTINUATION	$440,177
2020	2019	TEXAS A & M UNIVERSITY	400 HARVEY MITCHELL PKY S STE 300	COLLEGE STATION	TX	77845	BRAZOS	USA	Research Related to Deafness and Communication Disorders	000	21	12/20/2019	COMPETING CONTINUATION	$19,293
														Subtotal = $459,470

Issue Date FY: 2019 ( Subtotal = $458,922 )
2019	2019	TEXAS A & M UNIVERSITY	400 HARVEY MITCHELL PKY S STE 300	COLLEGE STATION	TX	77845	BRAZOS	USA	Research Related to Deafness and Communication Disorders	000	21	2/19/2019	COMPETING CONTINUATION	$459,469
2019	2017	TEXAS A & M UNIVERSITY	400 HARVEY MITCHELL PKY S STE 300	COLLEGE STATION	TX	77845	BRAZOS	USA	Research Related to Deafness and Communication Disorders	001	20	5/16/2019	NON-COMPETING CONTINUATION	-$547
														Subtotal = $458,922

Issue Date FY: 2018 ( Subtotal = $0 )
2018	2017	TEXAS A & M UNIVERSITY	400 HARVEY MITCHELL PKY S STE 300	COLLEGE STATION	TX	77845	BRAZOS	USA	Research Related to Deafness and Communication Disorders	000	20	7/26/2018	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2017 ( Subtotal = $302,818 )
2017	2017	TEXAS A & M UNIVERSITY	400 HARVEY MITCHELL PKY S STE 300	COLLEGE STATION	TX	77845	BRAZOS	USA	Research Related to Deafness and Communication Disorders	000	20	2/17/2017	NON-COMPETING CONTINUATION	$272,536
2017	2017	TEXAS A & M UNIVERSITY	400 HARVEY MITCHELL PKY S STE 300	COLLEGE STATION	TX	77845	BRAZOS	USA	Research Related to Deafness and Communication Disorders	001	20	5/24/2017	NON-COMPETING CONTINUATION	$30,282
														Subtotal = $302,818

Issue Date FY: 2016 ( Subtotal = $302,818 )
2016	2016	TEXAS A & M UNIVERSITY	400 HARVEY MITCHELL PARKWAY	COLLEGE STATION	TX	77845	BRAZOS	USA	Research Related to Deafness and Communication Disorders	000	19	2/24/2016	EXTENSION WITH OR WITHOUT FUNDS	$302,818
														Subtotal = $302,818

Issue Date FY: 2015 ( Subtotal = $299,789 )
2015	2015	TEXAS A & M UNIVERSITY	400 HARVEY MITCHELL PARKWAY	COLLEGE STATION	TX	77845	BRAZOS	USA	Research Related to Deafness and Communication Disorders	000	18	2/25/2015	NON-COMPETING CONTINUATION	$299,789
														Subtotal = $299,789

Issue Date FY: 2014 ( Subtotal = $302,818 )
2014	2014	TEXAS A & M UNIVERSITY	400 HARVEY MITCHELL PARKWAY	COLLEGE STATION	TX	77845	BRAZOS	USA	Research Related to Deafness and Communication Disorders	000	17	3/6/2014	NON-COMPETING CONTINUATION	$302,818
														Subtotal = $302,818

Issue Date FY: 2013 ( Subtotal = $302,818 )
2013	2013	TEXAS A & M UNIVERSITY	ADMIN BLDG, ROOM 210	COLLEGE STATION	TX	77843	BRAZOS	USA	Research Related to Deafness and Communication Disorders	000	16	2/1/2013	COMPETING CONTINUATION	$302,818
														Subtotal = $302,818

Issue Date FY: 2012 ( Subtotal = $290,160 )
2012	2012	TEXAS A & M RESEARCH FOUNDATION	400 Harvey Mitchell Parkway S,	COLLEGE STATION	TX	77845	BRAZOS	USA	Research Related to Deafness and Communication Disorders	000	15	3/23/2012	NON-COMPETING CONTINUATION	$290,160
														Subtotal = $290,160

Issue Date FY: 2011 ( Subtotal = $287,392 )
2011	2011	TEXAS A & M RESEARCH FOUNDATION	400 Harvey Mitchell Parkway S,	COLLEGE STATION	TX	77845	BRAZOS	USA	Research Related to Deafness and Communication Disorders	000	14	2/18/2011	NON-COMPETING CONTINUATION	$267,204
2011	2011	TEXAS A & M RESEARCH FOUNDATION	400 Harvey Mitchell Parkway S,	COLLEGE STATION	TX	77845	BRAZOS	USA	Research Related to Deafness and Communication Disorders	001	14	6/2/2011	NON-COMPETING CONTINUATION	$20,188
														Subtotal = $287,392

Issue Date FY: 2010 ( Subtotal = $296,893 )
2010	2010	TEXAS A & M RESEARCH FOUNDATION	400 Harvey Mitchell Parkway S,	COLLEGE STATION	TX	77845	BRAZOS	USA	Research Related to Deafness and Communication Disorders	000	13	3/5/2010	NON-COMPETING CONTINUATION	$296,893
														Subtotal = $296,893

Issue Date FY: 2009 ( Subtotal = $299,891 )
2009	2009	TEXAS A & M RESEARCH FOUNDATION	400 Harvey Mitchell Parkway S,	COLLEGE STATION	TX	77845	BRAZOS	USA	Research Related to Deafness and Communication Disorders	001	12	3/18/2009	NON-COMPETING CONTINUATION	$29,989
2009	2009	TEXAS A & M RESEARCH FOUNDATION	400 Harvey Mitchell Parkway S,	COLLEGE STATION	TX	77845	BRAZOS	USA	Research Related to Deafness and Communication Disorders	000	12	2/13/2009	NON-COMPETING CONTINUATION	$269,902
														Subtotal = $299,891

Issue Date FY: 2008 ( Subtotal = $299,891 )
2008	2008	TEXAS A & M UNIVERSITY RESEARCH FOUNDATION	400 Harvey Mitchell Parkway S,	COLLEGE STATION	TX	77845	BRAZOS	USA	Research Related to Deafness and Communication Disorders	000	11	2/25/2008	COMPETING CONTINUATION	$299,891
														Subtotal = $299,891

Issue Date FY: 2007 ( Subtotal = $307,444 )
2007	2007	TEXAS A & M UNIVERSITY RESEARCH FOUNDATION	POST OFFICE BOX 3578	COLLEGE STATION	TX	77843	BRAZOS	USA	Research Related to Deafness and Communication Disorders	000	10	2/28/2007	NON-COMPETING CONTINUATION	$307,444
														Subtotal = $307,444

Issue Date FY: 2006 ( Subtotal = $316,626 )
2006	2006	TEXAS A & M UNIVERSITY RESEARCH FOUNDATION	POST OFFICE BOX 3578	COLLEGE STATION	TX	77843	BRAZOS	USA	Research Related to Deafness and Communication Disorders	000	9	1/23/2006	NON-COMPETING CONTINUATION	$316,626
														Subtotal = $316,626

Issue Date FY: 2005 ( Subtotal = $324,245 )
2005	2005	TEXAS A & M UNIVERSITY RESEARCH FOUNDATION	POST OFFICE BOX 3578	COLLEGE STATION	TX	77843	BRAZOS	USA	Research Related to Deafness and Communication Disorders	000	8	1/22/2005	NON-COMPETING CONTINUATION	$324,245
														Subtotal = $324,245

Issue Date FY: 2004 ( Subtotal = $324,245 )
2004	2004	TEXAS A & M UNIVERSITY RESEARCH FOUNDATION	POST OFFICE BOX 3578	COLLEGE STATION	TX	77843	BRAZOS	USA	Research Related to Deafness and Communication Disorders	000	7	2/27/2004	NON-COMPETING CONTINUATION	$324,245
														Subtotal = $324,245

Issue Date FY: 2003 ( Subtotal = $324,245 ) (Continued on the next page)
Grand Total All Awards = $7,459,318

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Genetic Analysis of Inner Ear Development in Zebrafish

Award Number: R01DC003806

ORGANIZATION: NATIONAL INSTITUTE ON DEAFNESS AND OTHER COMMUNICATION DISORDERS

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

PERIOD OF PERFORMANCE START DATE: 05/01/1998

PERIOD OF PERFORMANCE END DATE: 03/31/2024

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