# Foxp-regulated signaling pathways in brain development  - Diversity

> **NIH NIH R01** · UT SOUTHWESTERN MEDICAL CENTER · 2022 · $80,234

## Abstract

RESEARCH AND TRAINING PLAN FOR RACHAEL VOLLMER
A. SUMMARY OF THE FUNDED GRANT
The parent grant (R01MH126481; funding period 06/01/21-05/31/2026) is titled: “Foxp-regulated signaling
pathways in brain development.” Two members of the FOXP family of transcription factors, FOXP1 and FOXP2,
have been linked to monogenetic forms of intellectual disability, autism spectrum disorders, and specific speech
and language deficits. Variants in FOXP1 or FOXP2 are among the most significant genes associated with
autism spectrum disorders. We previously showed that Foxp1 and Foxp2 both have significant contributions to
cortical and striatal development. We linked these developmental changes via studies of gene expression,
electrophysiology, and behaviors. We further identified non-cell-autonomous changes in gene expression using
newly available single-cell RNA-sequencing technology. Based on these data, the central hypothesis driving the
work in the parent grant and the proposed supplement is that Foxp1 and Foxp2 are key orchestrators of
transcriptional signaling cascades in a cell type-specific manner that are important for neuronal function and are
at risk in neurodevelopmental disorders such as autism. We propose to identify these cell type-specific
contributions in the developing cortex by using rodent models through two specific aims that will utilize snATAC-
seq: 1) Determine the cell type-specific gene regulatory programs orchestrated by Foxp1 in the developing
cortex; and 2) Determine the cell type-specific gene regulatory programs orchestrated by Foxp2 in the developing
cortex. Together, these aims will delineate the cell type contribution of both Foxp1 and Foxp2 to cortical
development. The rodent models and cell-type specific genomic datasets will provide insight into the basic
molecular mechanisms governing normal mammalian brain development. These research aims support the
mission of the NIMH to understand and develop treatments for mental disorders. Finally, the training plan that
we have described in this proposal will provide Ms. Vollmer with a cutting-edge skill set in neurogenomics.
Aims 1 and 2 of the parent grant are to identify the cell-type specific developmental transcriptional program
regulated by Foxp1 or Foxp2 in the mouse brain using single-nuclei RNA-sequencing (snRNA-seq) at several
time points. These experiments will utilize previously generated Foxp1 and Foxp2 cKO mice already generated
and published using Emx1.Cre (e.g. Araujo et al., Journal of Neuroscience 2017; Usui et al., Genes &
Development 2017; Co et al., Cerebral Cortex 2020). Our lab has also recently applied the approach of single-
nuclei ATAC-sequencing to uncover the cell type specific contributions of gene regulation and signaling
cascades (e.g. Berto et al., Nature Neuroscience 2021). Coupling this chromatin accessibility approach with
gene expression at the cell type level, should provide a new level of resolution for understanding how these
transcription factors ...

## Key facts

- **NIH application ID:** 10478320
- **Project number:** 3R01MH126481-01A1S1
- **Recipient organization:** UT SOUTHWESTERN MEDICAL CENTER
- **Principal Investigator:** Genevieve Konopka
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $80,234
- **Award type:** 3
- **Project period:** 2022-01-01 → 2024-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10478320

## Citation

> US National Institutes of Health, RePORTER application 10478320, Foxp-regulated signaling pathways in brain development  - Diversity (3R01MH126481-01A1S1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10478320. Licensed CC0.

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