# Defining links between an intellectual disability associated RNA-binding protein and planar cell polarity in neurodevelopment

> **NIH NIH F31** · EMORY UNIVERSITY · 2021 · $46,036

## Abstract

PROJECT SUMMARY:
Intellectual disability affects 1–3% of the worldwide population; these individuals have deficits in adaptive
functioning necessitating ongoing support to perform activities such as dressing, reading, and interpreting the
intentions of others. The cost of this support, for a single US patient, is approximately $1–2 million throughout
his or her lifespan1. The pathophysiology and etiology of intellectual disability has been difficult to elucidate due
to the heterogeneity in casual mutations2. Despite this complexity, mutations linked to intellectual disability tend
to accumulate in pathways relating to nervous system development, cellular metabolism, and microtubule based
movement and axonal transport3. Additionally, monogenic forms of intellectual disability provide direct insight
into defective cell biological processes that underlie intellectual disability. Our lab found that mutations in a
ubiquitously expressed zinc-finger, polyadenosine RNA-binding protein, ZC3H14, are linked to a form of
monogenic, non-syndromic autosomal recessive intellectual disability4. We developed a Drosophila
melanogaster model to investigate the role of dNab2, the fly ortholog to human ZC3H14. Loss of dNab2 results
in neuronal, survival, and locomotive phenotypes. Importantly, many of the phenotypes can be rescued by
transgenic expression of human ZC3H14 exclusively in neurons, implying a conservation of function from flies
to humans and feasibility in using dNab2 to model ZC3H14 function. Data generated from our fly model suggests
that dNab2 loss is critical in neurodevelopment, and that it may be regulating gene expression in neurons.
However, the identity of mRNA targets of dNab2 in neurons and the mechanism by which it regulates these
targets are key gaps in knowledge. Preliminary data suggest that dNab2 interacts functionally with multiple
components of the planar cell polarity (PCP) pathway. PCP is a non-canonical branch of Wnt signaling that
regulates axon guidance in the nervous system and tissue polarization in somatic tissue 5–8. Therefore, I will
directly test the hypothesis that dNab2 regulates PCP components to control neurite extension and guidance
during neurodevelopment. The Specific Aims of this project are: 1) define genetic dNab2:PCP interactions in
two neurodevelopmental contexts, 2) utilize a systems-level proteomic approach to identify dNab2 regulated
pathways in the brain, and 3) examine physical and functional interactions between dNab2 and PCP pathway
RNAs in vivo. Aim 1 utilizes Drosophila genetic tools to assess functional genetic interactions with dNab2 in two
neuronal cell types. Aim 2 uses network analyses, of a unique Drosophila proteomic dataset, to identify dNab2
regulated pathways. Aim 3 utilizes techniques to assess RNA localization and physical interaction with dNab2.
Successful completion of these aims will provide insight into how dNab2 regulates local gene expression to
impact neurodevelopment, and thus support...

## Key facts

- **NIH application ID:** 10130646
- **Project number:** 5F31NS110312-03
- **Recipient organization:** EMORY UNIVERSITY
- **Principal Investigator:** Edwin Corgiat
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $46,036
- **Award type:** 5
- **Project period:** 2019-04-01 → 2022-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10130646

## Citation

> US National Institutes of Health, RePORTER application 10130646, Defining links between an intellectual disability associated RNA-binding protein and planar cell polarity in neurodevelopment (5F31NS110312-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10130646. Licensed CC0.

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