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Slit Fragments Generate Diversity in Axon Guidance Signals

Award Number: R01NS114219
ORGANIZATION: NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 04/15/2021
PERIOD OF PERFORMANCE END DATE: 03/31/2025

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Slit Fragments Generate Diversity in Axon Guidance Signals - Axon guidance is the study of how developing nerves navigate in response to external signals. A remarkably small number of navigational signals have been identified, raising the question of how the complexity of the brain is generated. One solution is that a single ligand can signal in different ways either through the presence of different receptors or through processing that alters receptor binding. Slit is a large secreted protein that typically repels growing axons using Robo receptors. Slit is cleaved into two fragments, Slit-N and Slit-C, which display new biological activities in the nervous system and that in many other tissues. However, the role of the Slit fragments is controversial. The Slit-N fragment contains the Robo binding site and has been shown to be repel axons in in vitro culture systems and so is thought to be the active signaling molecule. Multiple lines of in vivo preliminary evidence in Drosophila suggest that only the full-length (Slit-FL) protein repels axons. This proposal takes an in vivo molecular genetic approach in flies and mice to separate the signaling of Slit-FL from that of the Slit fragments.These two systems will allow us to address the effects of Slit on axon growth, axon branching and regulated adhesion (fasciculation). This work will allow us to determine how a single signal can achieve different biological outcomes. The proposed work has implications for a diverse range of fields, including infectious disease, cancer and nerve regeneration.


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: 2024 ( Subtotal = $383,949 )
2024	2024	BOARD OF REGENTS OF THE NEVADA SYSTEM OF HIGHER ED	1664 N VIRGINIA ST # 285	RENO	NV	89557	WASHOE	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	001	4	4/11/2024	NON-COMPETING CONTINUATION	$27,708
2024	2024	BOARD OF REGENTS OF THE NEVADA SYSTEM OF HIGHER ED	1664 N VIRGINIA ST # 285	RENO	NV	89557	WASHOE	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	4	3/5/2024	NON-COMPETING CONTINUATION	$356,241
														Subtotal = $383,949

Issue Date FY: 2023 ( Subtotal = $395,823 )
2023	2023	NEVADA SYSTEM OF HIGHER EDUCATION	1664 N VIRGINIA ST	RENO	NV	89557	WASHOE	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	3	4/3/2023	NON-COMPETING CONTINUATION	$395,823
														Subtotal = $395,823

Issue Date FY: 2022 ( Subtotal = $395,823 )
2022	2022	NEVADA SYSTEM OF HIGHER EDUCATION	1664 N VIRGINIA ST	RENO	NV	89557	WASHOE	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	001	2	3/30/2022	NON-COMPETING CONTINUATION	$395,823
2022	2021	NEVADA SYSTEM OF HIGHER EDUCATION	1664 N VIRGINIA ST	RENO	NV	89557	WASHOE	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	1	2/11/2022	NEW	$0
														Subtotal = $395,823

Issue Date FY: 2021 ( Subtotal = $478,616 )
2021	2021	NEVADA SYSTEM OF HIGHER EDUCATION	1664 N VIRGINIA ST	RENO	NV	89557	WASHOE	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	001	1	9/19/2021	NEW	$70,418
2021	2021	NEVADA SYSTEM OF HIGHER EDUCATION	1664 N VIRGINIA ST	RENO	NV	89557	WASHOE	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	1	4/13/2021	NEW	$408,198
														Subtotal = $478,616

Grand Total All Awards = $1,654,211

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Slit Fragments Generate Diversity in Axon Guidance Signals

Award Number: R01NS114219

ORGANIZATION: NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 04/15/2021

PERIOD OF PERFORMANCE END DATE: 03/31/2025

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