# Functional investigations of Foxp1 and Foxp2 in Drd1 spiny projection neurons

> **NIH NIH F31** · UT SOUTHWESTERN MEDICAL CENTER · 2020 · $34,056

## Abstract

Project Summary
Individuals with mutations in either FOXP1 or FOXP2 have speech and language deficits and/or autism
spectrum disorder (ASD). Mutations of Foxp1 or Foxp2 in mice manifest in ASD-relevant behaviors, such as
repetitive behaviors, altered vocalizations, and impaired motor learning. Recent studies have identified
neuronal cell-types most likely to be disrupted across diverse genetic mutations linked to ASD, including deep
layer cortical neurons and striatal dopamine receptor 1 (Drd1) and dopamine receptor 2 (Drd2) expressing
spiny projections neurons (SPNs). FOXP1 is equivalently expressed in both Drd1 and Drd2 SPNs while
FOXP2 has enriched expression in Drd1 SPNs. Studies have found that a Drd2 specific knockout of Foxp1
results in reduced specification of Drd2 SPNs, increased intrinsic excitability of Drd2 SPNs, deficits in motor
learning, and altered striatal projection patterns. Conversely, Foxp1 expression in Drd1 SPNs is not required
for specification of Drd1 SPNs, motor learning or proper striatal projections. The enriched expression of Foxp2
in Drd1 SPNs may compensate for the loss of Foxp1. I therefore hypothesize that Foxp1 and Foxp2 have
compensatory functions in Drd1 SPNs. Using Drd1-targeted conditional knockout of Foxp1, Foxp2, or both, I
will test this hypothesis in two Aims. In Aim 2, I will test the requirement for either of these transcription factors
in motor relevant (rotarod, open field) and socially relevant (social interaction, pup vocalizations) behaviors. In
Aim 2, I will determine cell-specific gene expression changes with loss of either of these transcription factors by
comparing the results of single-nuclei RNA sequencing across multiple relevant time points. Successful
completion of these aims will provide a broader understanding of the role of vulnerable cell-types in brain
development and the pathophysiology of ASD. Moreover, I will gain a deeper insight into the functional cell-
type-specific roles of Foxp1 and Foxp2, two transcription factors that are at risk in monogenic causes of
neurodevelopmental disorders, including those that impact the development of speech and language.

## Key facts

- **NIH application ID:** 9991586
- **Project number:** 1F31NS117030-01
- **Recipient organization:** UT SOUTHWESTERN MEDICAL CENTER
- **Principal Investigator:** Newaz Ibrahim Ahmed
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $34,056
- **Award type:** 1
- **Project period:** 2020-09-01 → 2023-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9991586

## Citation

> US National Institutes of Health, RePORTER application 9991586, Functional investigations of Foxp1 and Foxp2 in Drd1 spiny projection neurons (1F31NS117030-01). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9991586. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*