# Regulation of mTOR signaling in the developing cerebral cortex as a point of convergence for multiple autism risk factors

> **NIH NIH R01** · SCRIPPS FLORIDA · 2020 · $480,000

## Abstract

PROJECT SUMMARY/ABSTRACT
PTEN and FMR1 are two susceptibility genes for autism spectrum disorder (ASD) that encode regulators of the
PI3K-Akt-mTOR pathway. Phosphorylation of ribosomal protein S6 (p-S6) is a downstream readout of mTOR
activity. Altered levels of p-S6 have been reported in the postmortem cerebral cortex of individuals with autism
and in mouse models of autism risk factors. However, it is not known when during development and in which
cell types dysregulation of p-S6 signaling occurs and whether this contributes to the symptoms of ASD. Our
goal is to identify common cell types and time windows in which p-S6 is dysregulated across two mouse
models of autism risk factors, Pten and Fmr1, and to study the relationship between p-S6 dysregulation and
social behavioral deficits. The novel hypothesis we develop here is that cell types that are normally enriched
for p-S6 in the developing brain are selectively vulnerable to overgrowth caused by Pten or Fmr1 mutations.
We propose to carry out this work by using an innovative combination of mapping the activity of a signaling
pathway (PI3K-Akt-mTOR/p-S6) key to cellular growth and ASD pathogenesis in the developing brain at
unprecedented spatiotemporal resolution, neuroanatomical tracing and behavioral phenotyping to determine
when and where dysregulation of p-S6 might contribute to the pathophysiology of ASD risk factors. In addition
to understanding molecular and cellular mechanism of social behavioral deficits, this will also test the
therapeutic potential of targeting mTOR/p-S6 signaling during a critical developmental time window as a
strategy for treating ASD.

## Key facts

- **NIH application ID:** 9888430
- **Project number:** 5R01MH108519-05
- **Recipient organization:** SCRIPPS FLORIDA
- **Principal Investigator:** Damon Theron Page
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $480,000
- **Award type:** 5
- **Project period:** 2016-07-01 → 2021-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9888430

## Citation

> US National Institutes of Health, RePORTER application 9888430, Regulation of mTOR signaling in the developing cerebral cortex as a point of convergence for multiple autism risk factors (5R01MH108519-05). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9888430. Licensed CC0.

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