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Cellular mechanisms of perivascular fibroblast development and dependence on PDGF signaling

Award Number: F31NS125875
ORGANIZATION: NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: FELLOWSHIP/SCHOLARSHIP/STUDENT LOANS
PERIOD OF PERFORMANCE START DATE: 12/01/2021
PERIOD OF PERFORMANCE END DATE: 04/30/2024

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Cellular mechanisms of perivascular fibroblast development and dependence on PDGF signaling - PROJECT SUMMARY Perivascular spaces (PVSs) are fluid-filled spaces surrounding vessels of the central nervous system, are thought to have important roles in maintenance of brain health, and are a unique niche for a variety of perivascular cell types. A cell type of particular interest is perivascular fibroblasts (PVFs) which are poorly characterized, and their functions are largely unknown. PVFs are known to reside on the outside the vascular smooth muscle layer of medium-to large-diameter vessels in the adult mouse central nervous system, and are primarily identified by expression of Collagen-1 and Platelet-derived growth factor receptor (PDGFR)a and PDGFRb. However, nearly nothing is known about the developmental origins, or the cellular and molecular mechanisms important for PVF development. Preliminary data suggests PVFs emerge from a population of cells in the meninges and gradually populate brain PVSs during postnatal development, but this has not yet been investigated further. These gap in knowledge is a major barrier to developing novel tools to investigate the role of PVFs in brain homeostasis and disease. The objective of this proposal is to investigate the developmental origins, cellular dynamics, and molecular signaling mechanisms involved in PVF development. In Aim 1, I will use a combination of transgenic mouse lines that label PVFs, optical tissue clearing, ex vivo imaging, and a multi-color lineage tracing reporter to investigate the cellular origins and dynamics of developing PVFs. In Aim 2, I will use intracisternal cerebrospinal fluid tracer assays to determine the relationship between the timing of PVF development and PVS function. Finally, in Aim 3 I will investigate PDGF signaling as a potential mechanism controlling PVF development. Together, this project will be the first to fully characterize how PVF development occurs and whether or not PDGF signaling is involved.


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 = -$3,118 )
2025	2024	THE REGENTS OF THE UNIVERSITY OF COLORADO	13001 E 17TH PL STE F428	AURORA	CO	80045	ADAMS	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	3	2/26/2025	NON-COMPETING CONTINUATION	-$3,118
														Subtotal = -$3,118

Issue Date FY: 2024 ( Subtotal = $23,109 )
2024	2024	REGENTS OF THE UNIVERSITY OF COLORADO, THE	13001 E 17TH PLACE F428	AURORA	CO	80045	ADAMS	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	3	12/1/2023	NON-COMPETING CONTINUATION	$38,743
2024	2024	THE REGENTS OF THE UNIVERSITY OF COLORADO	13001 E 17TH PL STE F428	AURORA	CO	80045	ADAMS	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	001	3	6/6/2024	NON-COMPETING CONTINUATION	-$15,634
														Subtotal = $23,109

Issue Date FY: 2023 ( Subtotal = $38,743 )
2023	2023	REGENTS OF THE UNIVERSITY OF COLORADO, THE	13001 E 17TH PLACE F428	AURORA	CO	80045	ADAMS	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	001	2	2/14/2023	NON-COMPETING CONTINUATION	$942
2023	2023	REGENTS OF THE UNIVERSITY OF COLORADO, THE	13001 E 17TH PLACE F428	AURORA	CO	80045	ADAMS	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	2	11/16/2022	NON-COMPETING CONTINUATION	$37,801
														Subtotal = $38,743

Issue Date FY: 2022 ( Subtotal = $37,801 )
2022	2022	REGENTS OF THE UNIVERSITY OF COLORADO, THE	13001 E 17TH PLACE F428	AURORA	CO	80045	ADAMS	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	1	11/19/2021	NEW	$37,085
2022	2022	REGENTS OF THE UNIVERSITY OF COLORADO, THE	13001 E 17TH PLACE F428	AURORA	CO	80045	ADAMS	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	001	1	11/19/2021	NEW	$0
2022	2022	REGENTS OF THE UNIVERSITY OF COLORADO, THE	13001 E 17TH PLACE F428	AURORA	CO	80045	ADAMS	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	002	1	4/27/2022	NEW	$717
2022	2022	REGENTS OF THE UNIVERSITY OF COLORADO, THE	13001 E 17TH PLACE F428	AURORA	CO	80045	ADAMS	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	003	1	6/23/2022	NEW	-$1
														Subtotal = $37,801

Grand Total All Awards = $96,535

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Cellular mechanisms of perivascular fibroblast development and dependence on PDGF signaling

Award Number: F31NS125875

ORGANIZATION: NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: FELLOWSHIP/SCHOLARSHIP/STUDENT LOANS

PERIOD OF PERFORMANCE START DATE: 12/01/2021

PERIOD OF PERFORMANCE END DATE: 04/30/2024

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