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Regulation of notochord vacuole biogenesis: investigating its role in spine formation and IVD Biology

Award Number: R01AR083346
ORGANIZATION: NATIONAL INSTITUTE OF ARTHRITIS & MUSCULOSKELETAL & SKIN DISEASES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 01/16/2024
PERIOD OF PERFORMANCE END DATE: 12/31/2028

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Regulation of notochord vacuole biogenesis: investigating its role in spine formation and IVD Biology - ABSTRACT The vertebral column or spine is the main structural element of the vertebrate body axis. It is assembled around the notochord, a conserved axial structure that provides developmental cues for the development of other organs and serves as a structural scaffold for the embryo in all chordates. Importantly, in vertebrates, the notochord also attracts osteoblast precursors that give rise to the vertebral bodies of the spine. The vertebrate notochord is composed of a core of highly conserved vacuolated cells that is surrounded by a thick extracellular matrix that acts as a corset for the notochord rod. Importantly, loss of notochord vacuole function has been shown to cause defects in vertebral formation and spine morphology that resemble congenital scoliosis (CS) in humans. While genetic and embryological evidence clearly showed that the structural role of the notochord is conserved, whether vacuolated cells function in vertebral patterning in mice as shown in zebrafish is not known. Moreover, following vertebral patterning, notochord vacuolated cells form the nucleus pulposus (NP) at the center of the intervertebral disc (IVD), where they remain until adulthood. However, little is known about the function of vacuolated cells within the IVD. Also not known are the mechanisms that regulate notochord vacuole biogenesis and integrity and how these are linked to IVD degeneration during aging. The proposed studies will investigate mechanisms regulating notochord vacuole biogenesis and function in zebrafish and mice and will investigate the role of notochord vacuoles in spine formation in mice. Altogether, these studies will bring important new insights into spine morphogenesis and the origin of pathologies such as CS and disc disease.


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 = $479,442 )
2026	2026	DUKE UNIVERSITY	2200 W MAIN ST	DURHAM	NC	27705	DURHAM	USA	Arthritis, Musculoskeletal and Skin Diseases Research	000	3	12/2/2025	NON-COMPETING CONTINUATION	$479,442
														Subtotal = $479,442

Issue Date FY: 2025 ( Subtotal = $530,090 )
2025	2025	DUKE UNIVERSITY	2200 W MAIN ST	DURHAM	NC	27705	DURHAM	USA	Arthritis, Musculoskeletal and Skin Diseases Research	001	2	6/6/2025	NON-COMPETING CONTINUATION	$38,252
2025	2025	DUKE UNIVERSITY	2200 W MAIN ST	DURHAM	NC	27705	DURHAM	USA	Arthritis, Musculoskeletal and Skin Diseases Research	000	2	12/18/2024	NON-COMPETING CONTINUATION	$491,838
														Subtotal = $530,090

Issue Date FY: 2024 ( Subtotal = $557,485 )
2024	2024	DUKE UNIVERSITY	2200 W MAIN ST	DURHAM	NC	27705	DURHAM	USA	Arthritis, Musculoskeletal and Skin Diseases Research	000	1	1/16/2024	NEW	$557,485
														Subtotal = $557,485

Grand Total All Awards = $1,567,017

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Regulation of notochord vacuole biogenesis: investigating its role in spine formation and IVD Biology

Award Number: R01AR083346

ORGANIZATION: NATIONAL INSTITUTE OF ARTHRITIS & MUSCULOSKELETAL & SKIN DISEASES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 01/16/2024

PERIOD OF PERFORMANCE END DATE: 12/31/2028

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