# Transcriptional regulation of neural circuit formation in intellectual disabilities

> **NIH NIH F32** · UNIVERSITY OF ROCHESTER · 2022 · $73,946

## Abstract

Project Summary
 Intellectual disabilities arise from disruption of normal brain function. ARX is a homeobox transcription
factor known to regulate brain development and patterning, which has been shown to cause an X-linked form of
intellectual disability and other syndromes associated with neurological deficits. Moreover, several mutations
have been identified in this gene, and there is a correlation between the class of mutation and the resulting
phenotype. Preliminary data shows that mutations in alr-1/ARX in Caenorhabditis elegans result in defects in
GABAergic neuronal differentiation, axon overextension, and synaptogenesis. Thus, the central hypothesis is
that different classes of alr-1/ARX variants cause specific syndromes by disrupting specific subsets of alr-1/ARX-
regulated gene networks, which in turn affects the formation and function of neural circuits. Using the powerful
genetics of the nematode C. elegans as a model and discovery system, alr-1/ARX cellular and molecular function
will be dissected to gain mechanistic insight into the role of alr-1/ARX in neural circuit formation and the
transcriptional regulation of this process. Additionally, how ARX disease-causing mutations disturb these
processes and results in abnormal wiring of the nervous system will be explored.
 The findings will identify novel candidate genes that may be disrupted in patients with intellectual
disabilities and more importantly, the regulatory network responsible. Understanding how their disruption leads
to the phenotype is necessary to further elucidate other genes responsible for other unknown cases of ID given
that these are likely targets or co-regulators of alr-1/ARX. These findings will establish the ground for the
translation of the basic science results to vertebrates and eventually to the bedside. The University of Rochester
and its Endocrinology division provide a unique collaborative environment of excellence in basic, clinical and
translational research, and is invested in the success of early career scientists. The training plan capitalizes on
the applicant’s strong research background and long-standing interest neural circuit formation combined with the
mentoring of Dr. Portman. He will obtain training in the transcriptomics field, and master cutting-edge technology
in cell-sorting, RNA-sequencing and Cut&Tag-sequencing, while being mentored by leaders in the field.
Ultimately, the postdoctoral fellowship will allow the fellow to expand his scientific training and create an
independent line of investigation needed for transitioning to an independent physician-scientist career.

## Key facts

- **NIH application ID:** 10433857
- **Project number:** 5F32HD105323-02
- **Recipient organization:** UNIVERSITY OF ROCHESTER
- **Principal Investigator:** Carlos Antonio Diaz-Balzac
- **Activity code:** F32 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $73,946
- **Award type:** 5
- **Project period:** 2021-04-26 → 2024-04-25

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10433857

## Citation

> US National Institutes of Health, RePORTER application 10433857, Transcriptional regulation of neural circuit formation in intellectual disabilities (5F32HD105323-02). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10433857. Licensed CC0.

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