# Elucidating the Roles of Mbd3 during Cerebellar Development

> **NIH NIH F30** · WASHINGTON UNIVERSITY · 2020 · $45,618

## Abstract

Chromatin remodeling complexes are single- or multi-subunit protein complexes that are thought to regulate
transcription by modifying the composition, occupancy, or positioning of nucleosomes along the genome. Many
mutations in chromatin remodeling complex subunits are associated with intellectual disability and autism,
suggesting that neurons may require strict chromatin regulation to establish neuronal connectivity. Therefore,
understanding how chromatin remodeling regulates circuit development is crucial to discovering treatments for
these neurodevelopmental disorders.
Like many other chromatin remodeling complexes, mutations in subunits of the nucleosome remodeling and
deacetylase (NuRD) complex are associated with intellectual disability and autism. Unique among chromatin
remodeling complexes though, the NuRD complex is endowed with two enzymes: a chromatin remodeling
ATPase and a histone deacetylase, through Chd3/4 and Hdac1/2, respectively. Previously, the Bonni
laboratory discovered that Chd4 is required to establish connectivity of the cerebellar granule neuron into the
circuit of the cerebellar cortex. Chd4 regulates both the elimination of dendrites and the formation of
presynaptic boutons during granule neuron development. These observations raise vital questions about how
NuRD complex function leads to granule neuron connectivity.
Various scaffold subunits are thought to regulate the function of the complex, but only Mbd3 is required for
complex assembly. Preliminary evidence suggests that Mbd3 controls transcription of a subset of Chd4-
dependent genes in the cerebellum, potentially by regulating Chd4 function directly at these sites. To clarify
how Mbd3 regulates neuronal connectivity, this proposal will define roles for Mbd3 in (1) granule neuron
connectivity with in vivo electroporation and imaging approaches; and (2) Chd4-dependent transcription with
chromatin immunoprecipitation (ChIP)-seq and bioinformatic analyses.
Clarifying these mechanisms will develop fundamental insight into Mbd3’s role in NuRD complex function and
brain development, illuminating potential mechanisms of neurodevelopmental disorder.

## Key facts

- **NIH application ID:** 9971546
- **Project number:** 5F30HD094447-03
- **Recipient organization:** WASHINGTON UNIVERSITY
- **Principal Investigator:** Jared Vega Goodman
- **Activity code:** F30 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $45,618
- **Award type:** 5
- **Project period:** 2018-08-01 → 2021-05-21

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9971546

## Citation

> US National Institutes of Health, RePORTER application 9971546, Elucidating the Roles of Mbd3 during Cerebellar Development (5F30HD094447-03). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9971546. Licensed CC0.

---

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