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Gene networks in cochlear patterning

Award Number: R21DC016376
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: 07/01/2017
PERIOD OF PERFORMANCE END DATE: 06/30/2020

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Gene networks in cochlear patterning - Abstract Understanding the precise patterning of the cochlea across the radial axis is crucial as it confers neural processing by afferent and efferent neurons enabling animals to process sound. An important aspect of this is determining how a pool of progenitors are instructed to differentiate into sub- compartments and several cell types of the cochlea under the control of diffusible factors. Wnts are Bmps are two major families of secreted factors that operate across the radial axis to partition the cochlea and specify cell fates. Wnts are widely known for their ability to re-program quiescent cells to re-enter the cell cycle, but they are also important for cochlear patterning. Our data show that manipulation of Wnt signaling affected cochlear patterning. In the organ of Corti, pharmacological activation of the Wnt pathway on E12.5 cochlear explants showed an increase in the medial compartment and inner hair cells, while suppressing the lateral compartment and outer hair cells. Several known Wnt genes were up regulated at one stage, but were differentially regulated at other stages. This implicates the action of feedback and feedforward networks on target genes. The spatiotemporal expression of target genes, can aid in predicting these gene networks that determine patterning. Aim 1 will test putative Wnt-mediated gene regulatory networks operating in the cochlea. Activation of the Wnt pathway also repressed Bmp4 expression, which is required for specifying the lateral compartment and fates; thus, the Wnt pathway engages in crosstalk with the Bmp pathway to generate the highly specialized patterning of the organ of Corti. Aim 2 will investigate molecular mechanisms underlying Wnt-Bmp crosstalk. These studies are specifically designed to identify and validate sub circuits of a larger gene regulatory network regulating radial patterning of the developing mouse cochlea.


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: 2021 ( Subtotal = $0 )
2021	2019	THE JACKSON LABORATORY	600 MAIN ST	BAR HARBOR	ME	04609	HANCOCK	USA	Research Related to Deafness and Communication Disorders	000	3	12/5/2020	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2019 ( Subtotal = $155,000 )
2019	2019	THE JACKSON LABORATORY	600 MAIN ST	BAR HARBOR	ME	04609	HANCOCK	USA	Research Related to Deafness and Communication Disorders	003	3	7/17/2019	NON-COMPETING CONTINUATION	$155,000
2019	2018	THE JACKSON LABORATORY	600 MAIN ST	BAR HARBOR	ME	04609	HANCOCK	USA	Research Related to Deafness and Communication Disorders	000	2	2/5/2019	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$0
2019	2018	THE JACKSON LABORATORY	600 MAIN ST	BAR HARBOR	ME	04609	HANCOCK	USA	Research Related to Deafness and Communication Disorders	002	2	2/12/2019	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$45,814
2019	2017	PURDUE UNIVERSITY	155 S GRANT ST	WEST LAFAYETTE	IN	47907	TIPPECANOE	USA	Research Related to Deafness and Communication Disorders	001	1	2/12/2019	NEW	-$45,814
														Subtotal = $155,000

Issue Date FY: 2018 ( Subtotal = $155,000 )
2018	2018	THE JACKSON LABORATORY	600 MAIN ST	BAR HARBOR	ME	04609	HANCOCK	USA	Research Related to Deafness and Communication Disorders	001	2	6/27/2018	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$155,000
2018	2017	PURDUE UNIVERSITY	401 SOUTH GRANT ST	WEST LAFAYETTE	IN	47907	TIPPECANOE	USA	Research Related to Deafness and Communication Disorders	000	1	6/25/2018	NEW	$0
														Subtotal = $155,000

Issue Date FY: 2017 ( Subtotal = $155,000 )
2017	2017	PURDUE UNIVERSITY	401 SOUTH GRANT ST	WEST LAFAYETTE	IN	47907	TIPPECANOE	USA	Research Related to Deafness and Communication Disorders	000	1	5/31/2017	NEW	$155,000
														Subtotal = $155,000

Grand Total All Awards = $465,000

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Gene networks in cochlear patterning

Award Number: R21DC016376

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: 07/01/2017

PERIOD OF PERFORMANCE END DATE: 06/30/2020

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