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Cellular and Molecular Mechanisms Underlying Neuronal Type-specific Axon Regeneration

Award Number: R01NS126821
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: 02/06/2023
PERIOD OF PERFORMANCE END DATE: 01/31/2028

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Cellular and Molecular Mechanisms Underlying Neuronal Type-specific Axon Regeneration - Project description Failure in axon regeneration after nervous system lesion is a major roadblock for functional recovery. Axon regeneration is controlled by both intrinsic and extrinsic cues from both neurons and surrounding glial environment. However, our understanding of glial control of axon regeneration remains incomplete. Here, we investigate axon regeneration of well-defined sensory neurons in Drosophila larvae. This in vivo model offers a powerful opportunity to investigate axon regeneration with single-cell resolution and genetic tractability. Our pilot study has made novel findings by discovering a critical involvement of glia-neuron interactions, in the form of gliotransmission, in specifying axon regenerative differences of neuron types. Based on these findings, we hypothesize that gliotransmission orchestrates neuron type-specific axon regeneration. Specifically, we propose that axotomy activates Ca2+ signals in glial cells to elicit gliotransmission, leading to accumulation of extracellular ATP. ATP is then converted by ecto-5’- nucleotidases to adenosine before activating adenosine receptors in the select neuron type, resulting in neuron type-specific Ca2+ signals and axon regeneration. In this project, we will leverage the power of Drosophila genetics and combine it with multidisciplinary approaches to test this hypothesis. Because axon regeneration mechanisms are conserved, our findings will likely be relevant to other species including 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: 2025 ( Subtotal = $376,875 )
2025	2025	UNIVERSITY OF MASSACHUSETTS MEDICAL SCHOOL	55 LAKE AVE N	WORCESTER	MA	01655	WORCESTER	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	3	1/16/2025	NON-COMPETING CONTINUATION	$376,875
														Subtotal = $376,875

Issue Date FY: 2024 ( Subtotal = $406,188 )
2024	2024	UNIVERSITY OF MASSACHUSETTS MEDICAL SCHOOL	55 LAKE AVE N	WORCESTER	MA	01655	WORCESTER	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	001	2	4/9/2024	NON-COMPETING CONTINUATION	$29,313
2024	2024	UNIVERSITY OF MASSACHUSETTS MEDICAL SCHOOL	55 LAKE AVE N	WORCESTER	MA	01655	WORCESTER	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	2	2/12/2024	NON-COMPETING CONTINUATION	$376,875
														Subtotal = $406,188

Issue Date FY: 2023 ( Subtotal = $418,750 )
2023	2023	UNIVERSITY OF MASSACHUSETTS MEDICAL SCHOOL	55 LAKE AVE N	WORCESTER	MA	01655	WORCESTER	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	1	2/3/2023	NEW	$418,750
														Subtotal = $418,750

Grand Total All Awards = $1,201,813

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Cellular and Molecular Mechanisms Underlying Neuronal Type-specific Axon Regeneration

Award Number: R01NS126821

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: 02/06/2023

PERIOD OF PERFORMANCE END DATE: 01/31/2028

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