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Molecular mechanisms underlying morphogenesis of the tectorial membrane

Award Number: R01DC018814
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: 02/09/2021
PERIOD OF PERFORMANCE END DATE: 01/31/2026

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Molecular mechanisms underlying morphogenesis of the tectorial membrane - PROJECT SUMMARY/ABSTRACT The tectorial membrane (TM) is an extracellular matrix (ECM) that lies over the organ of Corti. The TM plays important roles in frequency selection, propagation, and amplification of sound waves. Malformation of the TM causes hereditary hearing deficits. Since the TM is an acellular structure, its unique properties arise from the matrix architecture. The TM exhibits sophisticated ultrastructural features and domain-specific patterns of matrix organization. However, the mechanisms by which the specific matrix architectures are organized outside of cells are unknown. Is it determined by its molecular composition and/or mode of organization? We observed that surface-tethering of a-tectorin/TECTA via a glycosylphosphatidylinositol (GPI)-anchor is required to prevent diffusion of secreted TM components into the luminal space of the scala media and to form the TM matrix on the apical surface of TM-producing cells. The release of TECTA plays a critical role in the growth of the TM layers. Our in vitro assays show that TECTA is released from the producing cells by multiple mechanisms and that the different forms of TECTA released by these distinct mechanisms show unique multimerization activities. In this proposal, we will determine the molecular mechanism by which TECTA mediates the organization of specific TM architecture. We will characterize molecular dynamics that occur during the matrix maturation. Our results will provide the first evidence of how a complex ECM structure is established and matures in the extracellular space at the molecular level. This will provide novel insights into the process of morphogenesis as well as the mechanism of hereditary and age-related hearing deficits.


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: 2025 ( Subtotal = $324,063 )
2025	2025	UNIVERSITY OF UTAH	201 PRESIDENTS CIR	SALT LAKE CITY	UT	84112	SALT LAKE	USA	Research Related to Deafness and Communication Disorders	000	5	1/21/2025	NON-COMPETING CONTINUATION	$291,656
2025	2025	UNIVERSITY OF UTAH	201 PRESIDENTS CIR	SALT LAKE CITY	UT	84112	SALT LAKE	USA	Research Related to Deafness and Communication Disorders	001	5	6/13/2025	NON-COMPETING CONTINUATION	$32,407
														Subtotal = $324,063

Issue Date FY: 2024 ( Subtotal = $324,063 )
2024	2024	UNIVERSITY OF UTAH	201 PRESIDENTS CIR	SALT LAKE CITY	UT	84112	SALT LAKE	USA	Research Related to Deafness and Communication Disorders	000	4	1/18/2024	NON-COMPETING CONTINUATION	$291,656
2024	2024	UNIVERSITY OF UTAH	201 PRESIDENTS CIR	SALT LAKE CITY	UT	84112	SALT LAKE	USA	Research Related to Deafness and Communication Disorders	001	4	5/3/2024	NON-COMPETING CONTINUATION	$32,407
														Subtotal = $324,063

Issue Date FY: 2023 ( Subtotal = $324,063 )
2023	2023	UNIVERSITY OF UTAH, THE	201 PRESIDENTS CIR	SALT LAKE CITY	UT	84112	SALT LAKE	USA	Research Related to Deafness and Communication Disorders	000	3	1/19/2023	NON-COMPETING CONTINUATION	$324,063
														Subtotal = $324,063

Issue Date FY: 2022 ( Subtotal = $324,063 )
2022	2022	UNIVERSITY OF UTAH, THE	201 PRESIDENTS CIR	SALT LAKE CITY	UT	84112	SALT LAKE	USA	Research Related to Deafness and Communication Disorders	000	2	1/18/2022	NON-COMPETING CONTINUATION	$291,656
2022	2022	UNIVERSITY OF UTAH, THE	201 PRESIDENTS CIR	SALT LAKE CITY	UT	84112	SALT LAKE	USA	Research Related to Deafness and Communication Disorders	001	2	4/21/2022	NON-COMPETING CONTINUATION	$32,407
														Subtotal = $324,063

Issue Date FY: 2021 ( Subtotal = $324,063 )
2021	2021	UNIVERSITY OF UTAH, THE	201 PRESIDENTS CIR	SALT LAKE CITY	UT	84112	SALT LAKE	USA	Research Related to Deafness and Communication Disorders	000	1	2/9/2021	NEW	$324,063
														Subtotal = $324,063

Grand Total All Awards = $1,620,315

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Molecular mechanisms underlying morphogenesis of the tectorial membrane

Award Number: R01DC018814

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: 02/09/2021

PERIOD OF PERFORMANCE END DATE: 01/31/2026

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