Investigating molecular mechanisms of meningeal fibroblast development
Active Project Grant Awarded Last action
- Award ID
- F31NS151592
- Recipient
-
The Regents Of The University Of Colorado UEI MW8JHK6ZYEX8 Part of The Regents Of The University Of Colorado
- Awarding agency
-
National Institute of Neurological Disorders and Stroke
National Institutes of Health, Department of Health and Human Services
- Obligated
- $38,044
Award facts
- Assistance listing
- 93.853 Extramural Research Programs in the Neurosciences and Neurological Disorders
- Completion date 0% complete
- Place of performance
- Aurora, CO 80045, USA
Award details come from USAspending.gov.
Description
- Abstract
- The meninges are a three layer structure that surrounds the central nervous system (CNS). Each layer contains transcriptionally distinct fibroblasts that play a vital role in CNS development by producing paracrine factors that drive neurogenesis and neuronal migration. The meninges and meningeal fibroblasts develop from one layer into three between embryonic days 10 (E10) and 14 (E14). IT has been established by our group and others that the transcription factor FOXC1 is required for this process and that FOXC1 mutant mouse models to not make layer specific meningeal fibroblast and have a lengthened neocortex. There is still a GAP in knowledge regarding how FOXC1 transcriptionally regulates meningeal fibroblast development as well what other molecular mechanisms are contributing to their development. Using a multiomic approach, i performed single nuclei RNA sequencing and single nuclei atac sequencing on E12 meninges to characterize the developmental timing of meningeal fibroblast development. My analyses have implicated that notch, BMP, and WNT signaling are involved in the specification of dural and pial fibroblasts. The objective of this proposal is to test if the notch, BMP, and WNT signaling pathways are contributing to meningeal fibroblast specification. In aim 1, i will generate three different mouse models with disrupted notch, BMP, and WNT signaling and perform in situ hybridization for layer specific transcriptional markers and see how this impacts the development of meningeal fibroblasts, neocortical development and calvarium development. In aim 2, i will focus on the regulatory role FOXC1 plays in the developmental process. In aim 1, i expect to find that notch, BMP, and WNT signaling are required for meningeal fibroblast specification. I will test if these pathways are disrupted in FOXC1 mutant mice, indicating that FOXC1 transcriptionally regulates these pathways. I will also determine where FOXC1 is binding in meningeal fibroblasts by performing cut & run and i will ascertain how gene expression and chromatin accessibility changes in meningeal fibroblasts between FOXC1 mutants and controls. Results from this project will reveal the mechanism necessary for normal meningeal fibroblast development.
Quick answers
Who received award F31NS151592?
F31NS151592 was awarded to The Regents Of The University Of Colorado by National Institute of Neurological Disorders and Stroke (National Institutes of Health) on February 26, 2027.
How much is award F31NS151592 worth?
$38,044 has been obligated on F31NS151592.
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