# The Foxp2 Influence on the Developing Auditory Pathway

> **NIH NIH F30** · UT SOUTHWESTERN MEDICAL CENTER · 2024 · $40,127

## Abstract

Sensory hyper- and hyposensitivity is a feature of neurodevelopmental disorders (NDDs), including autism
spectrum disorder (ASD). It can cause significant quality of life deficits through maladaptive sensory seeking and
avoiding behaviors. Foxp2 is a transcription factor expressed in the developing and mature brain. Mutations in
human FOXP2 have been linked to NDDs, ASD, and most notably speech and language disorders. Foxp2 has
selective expression in the brain including several areas involved in the auditory processing pathway including
layer VI corticothalamic projection neurons (CThPNs), in the cells in auditory cortex (AC) and cells in the inferior
colliculi (IC), a midbrain region crucial in auditory processing. Preliminary studies of the loss of Foxp2 in the
mouse IC show sensory gating deficits and cell population changes. However, the role for Foxp2 in the
developing and mature auditory sensory areas of the neocortex and brainstem, remains to be fully elucidated.
This proposal will address the role of Foxp2 in the developing AC and IC at single nuclei resolution to identify
downstream targets of and chromatin accessibility changes by Foxp2. With two regions, single nuclei
transcriptomic (snRNA-seq) and chromatin accessibility data (snATAC-seq) can identify unique and overlapping
genes and regulatory pathways which will help elucidate the role of Foxp2 in each region and region-specific cell
types in sensory processing. Ex vivo recordings will also identify changes in cell and circuit function with
electrophysiological recordings of single and paired cells to find circuit and synapse dysregulation and cellular
excitability alterations caused by the loss of Foxp2. I hypothesize that Foxp2 has a critical role in sensory
processing mediated through proper cortical and IC neural development. I predict Foxp2 regulates cell
type-specific transcriptional networks with both cell autonomous and non-cell autonomous effects in gene
regulation, chromatin accessibility, and influences cell and circuit dysfunction underlying the sensory processing
deficits seen in ASD and other NDDs as a risk gene. Aim 1 will utilize paired snRNA-seq and snATAC-seq to
determine how conditional deletion of Foxp2 affects cellular expression profiles of the AC and IC across
development. I hypothesize that Foxp2-cKO will have ASD-related gene dysregulation, chromatin accessibility
patterns, and cell type imbalances in cortical and IC neurons. Aim 2 will assess the cortical and IC cell and circuit
electrophysiology regulated by Foxp2. I hypothesize that the loss of Foxp2 expression in the cortex and IC will
have circuit and cellular level changes that will result in changes in intrinsic excitability, interfering with thalamic
signaling. These data will be generated through whole cell recordings to determine the intrinsic electrophysiologic
properties of both AC Layer VI CThPNs and IC excitatory neurons as well as paired stimulation and recording of
IC and AC projections and ...

## Key facts

- **NIH application ID:** 10996801
- **Project number:** 1F30DC022213-01
- **Recipient organization:** UT SOUTHWESTERN MEDICAL CENTER
- **Principal Investigator:** Miranda Jankovic
- **Activity code:** F30 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $40,127
- **Award type:** 1
- **Project period:** 2024-06-01 → 2027-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10996801

## Citation

> US National Institutes of Health, RePORTER application 10996801, The Foxp2 Influence on the Developing Auditory Pathway (1F30DC022213-01). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10996801. Licensed CC0.

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