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Meninges Specification and Cellular Crosstalk to the Developing Brain

Award Number: F31NS130940
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: 12/07/2022
PERIOD OF PERFORMANCE END DATE: 10/06/2025

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Meninges Specification and Cellular Crosstalk to the Developing Brain - PROJECT SUMMARY Development of the central nervous system (CNS) requires precise intercellular ‘crosstalk’ between neural cells and non-neural cells. Fibroblasts in the meninges are a non-neural cell that substantially influences brain development, in large part via secreted factors that guide neuronal migration and neurogenesis. This is underscored by significant defects in CNS development observed in mice and humans with mutations in FOXC1, a transcription factor expressed by meningeal fibroblasts but not any neural cells. However much remains unknown about how factors from the meninges activate or inhibit molecular signaling pathways in neural cells to influence developmental processes. Filling these gaps in knowledge would significantly improve our understanding of the homeostatic function of the meninges and the pathology that occurs in neurodevelopmental disorders. Foxc1 mutants do not have normal meningeal fibroblasts over the forebrain, have increased apical progenitor self-renewal and reduced neuron production leading to neocortical lengthening, linked in part to lack of meninges derived retinoic acid. However, it is not known what aberrant signaling pathways in Foxc1 mutant apical progenitors promote increased self-renewal and how this is connected to a reduction of meninges derived factors like retinoic acid. The objective of this proposal is to investigate how meninges derived factors regulate molecular signaling to control neurogenesis in the neocortex. Using spatial transcriptomics on embryonic Foxc1- KO tissue sections, I have identified elevated Notch signaling, known to promote stem cell self-renewal, in Foxc1- KO neocortical progenitors. In Aim 1, I will use global and targeted approaches to inhibit Notch signaling in Foxc1-KO animals and test if this improves neocortical neurogenesis in these mutants. In Aim 2, I will test is meningeal derived retinoic acid or other factors produced by the meninges modulate Notch signaling in neocortical progenitors to promote neurogenesis. Results from this project will provide important insight into molecular mechanisms for meninges-brain signaling required for normal development.


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 = $35,748 )
2025	2025	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	11/29/2024	NON-COMPETING CONTINUATION	$35,748
														Subtotal = $35,748

Issue Date FY: 2024 ( Subtotal = $40,235 )
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	002	2	6/17/2024	NON-COMPETING CONTINUATION	$1,280
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	001	2	12/4/2023	NON-COMPETING CONTINUATION	$38,955
2024	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	1	11/22/2023	NEW	$0
														Subtotal = $40,235

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	000	1	12/7/2022	NEW	$37,801
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	1	2/14/2023	NEW	$942
														Subtotal = $38,743

Grand Total All Awards = $114,726

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Meninges Specification and Cellular Crosstalk to the Developing Brain

Award Number: F31NS130940

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: 12/07/2022

PERIOD OF PERFORMANCE END DATE: 10/06/2025

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