# Arx Associated Transcriptional Networks in Neocortical Development

> **NIH NIH R01** · BRIGHAM AND WOMEN'S HOSPITAL · 2021 · $128,179

## Abstract

PROJECT SUMMARY
Neurodevelopmental disorders (intellectual disability, epilepsy, autism, attention deficit, etc.) are
diagnosed in 1 in 6 children in the US according to the report from the Center for Disease Control and
Prevention. Despite this high frequency, the molecular and cellular basis for only a few disorders
have been elucidated, the basis of most remains unknown. Interestingly, patients with mutations in
ARX exhibit nearly all of these features. However, the developmental mechanism by which ARX
mutations result in this wide spectrum of problems is incompletely understood. Our prior work has
demonstrated that ARX is expressed in two different neural progenitor populations during forebrain
development and that it plays distinct roles in each population by regulating different subsets of
genes. Furthermore, we have shown that the loss of Arx from each progenitor population accounts for
specific components of the mouse and human phenotypes. In this proposal, building on our data from
the past ten years, we seek to understand how ARX regulates different subset of genes in different
progenitor populations. First, the proposed studies will focus on identification of ARX-interacting
transcription factors (or co-factors) and their down-stream target genes co-regulated by ARX in each
cell population. The combination of proteomics and genomics approach as well as systematic
network analysis will identify the key target genes predicted to play crucial roles in each progenitor
specific, ARX-mediated cellular functions that we previously defined. Second, the proposed studies
will elucidate the mechanism(s) by which ARX and ARX-associated network influence cortical
progenitor proliferation and patterning. Third, the proposed studies will delineate the role of ARX and
ARX-associated network in GE progenitor cell development. These studies are expected to provide a
greater understanding of how ARX functions in normal and abnormal brain development, and will
contribute to our understanding of the pathogenesis of such common disorders in children as
intellectual disabilities, epilepsy, autism, and structural anomalies of the brain.

## Key facts

- **NIH application ID:** 10158549
- **Project number:** 5R01NS100007-04
- **Recipient organization:** BRIGHAM AND WOMEN'S HOSPITAL
- **Principal Investigator:** Jeffrey A Golden
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $128,179
- **Award type:** 5
- **Project period:** 2018-05-01 → 2021-08-01

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10158549

## Citation

> US National Institutes of Health, RePORTER application 10158549, Arx Associated Transcriptional Networks in Neocortical Development (5R01NS100007-04). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10158549. Licensed CC0.

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