# Investigating the role of Growth-differentiation factor 11 in neurodevelopmental and MECP2-related disorders

> **NIH NIH F32** · BAYLOR COLLEGE OF MEDICINE · 2020 · $69,306

## Abstract

PROJECT SUMMARY
 Loss-of-function mutations or duplication in methyl-CpG binding protein 2 (MECP2) cause two severe
neurodevelopmental disorders: Rett syndrome and MECP2 duplication syndrome, respectively. While the
genetic cause of these disorders is known, the mechanism by which disruption in MECP2 leads to pathogenesis
is unknown; this has prevented the development of targeted therapies. Treatment with secreted factors has
shown some efficacy in preclinical mouse models of MECP2-disorders. To identify candidate secreted factors
misregulated by MeCP2, transcriptome profiles collected from Mecp2-null mouse models were evaluated, and
Growth differentiation factor 11 (GDF11) was identified as a growth factor sensitive to MECP2-levels. GDF11 is
downregulated in Mecp2-null models, while upregulated in MECP2-transgenic models. The opposing regulation
of GDF11 by MECP2 implicates GDF11 misregulation as one potential shared mechanism between Rett and
MECP2 duplication syndromes. GDF11 is a transforming growth factor beta family ligand that is a critical
patterning morphogen for the skeletal system. However, despite broad expression throughout the brain, the role
of GDF11 in brain development is unknown.
The work proposed in this fellowship will test the hypothesis that GDF11 is a key morphogen for brain
development, and that its misregulation in models of MECP2-disorders contributes to MECP2-disorder
phenotypes. This hypothesis will be tested through the following specific aims:
 1. Test if modulating brain specific dose of GDF11 by viral or genetic methods itself causes aberrant
 neurological phenotypes.
 2. Test if normalization of GDF11 levels rescues neurological phenotypes seen in mouse models of MECP2-
disorders.
 3. Test the regulatory relationship between MECP2 and GDF11 by modeling the temporal changes in the
 transcriptome after perturbation of MECP2-levels to identify primary gene expression changes.
The results from this fellowship will address three key questions in the field: 1) is GDF11 dose important in brain
development, 2) does rescue of GDF11-levels ameliorate phenotypes in mouse models of MECP2-disorders,
and 3) what are the primary gene expression changes that occur upon modulation of MECP2 levels.

## Key facts

- **NIH application ID:** 10022128
- **Project number:** 5F32HD100048-02
- **Recipient organization:** BAYLOR COLLEGE OF MEDICINE
- **Principal Investigator:** Sameer Bajikar
- **Activity code:** F32 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $69,306
- **Award type:** 5
- **Project period:** 2019-09-10 → 2022-03-09

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10022128

## Citation

> US National Institutes of Health, RePORTER application 10022128, Investigating the role of Growth-differentiation factor 11 in neurodevelopmental and MECP2-related disorders (5F32HD100048-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10022128. Licensed CC0.

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