# The role of Myt1l in the developing and adult mouse brain

> **NIH NIH R01** · STANFORD UNIVERSITY · 2020 · $734,935

## Abstract

We found that the three transcription factors Ascl1, Myt1-like (Myt1l), and Brn2 can reprogram fibroblasts
directly into functional neurons and are thus powerful neuronal lineage determination factors. Ascl1 and Brn2
are well studied genes. Myt1l on the other hand is a fairly uncharacterized zinc finger domain containting
protein predicted to be a transcription factor. It has a remarkably unique expression pattern: it is expressed in
virtually all neurons, but at the same time is also specific for neurons, to our knowledge the only transcription
factor known to be specific and pan-neuronal at the same time. Independent of the reprogramming work,
recent sequencing studies showed that MYT1L is frequently mutated in neuropsychiatric disease including
autism and schizophrenia. Nevertheless, very little is known about this gene. Not even a mouse knock-out has
been reported yet. We have therefore begun to investigate Myt1l's role in reprogramming and during normal
development. Our first insights about its molecular function suggest that Myt1l is important for neuronal
reprogramming and normal embryonic neurogenesis acting predominantly by transcriptional repression of non-
neuronal lineage programs.
The goal of this research project is to better understand the role of Myt1l in neurons after neurogenesis
is completed. We propose to investigate its role on the molecular, cellular circuit, and behavioral level using the
mouse as model system. We have intriguing preliminary data that about a third of high confidence autism-
causing chromatin factors are also candidate binding partners of Myt1l. This suggests that all these mutations
might converge on a hypothetical Myt1l-associated “chromatin pathway” which is dysfunctional in at least
subset of autism. This project will test this hypothesis and evaluate whether interference with the members of
this chromatin “pathway” might rectify molecular, cellular or behavioral phenotypes caused by Myt1l deletion.
Since chromatin modifying enzymes are in principle pharmacologically tractable the hope would be that a
functional intervention of such chromatin factors may be of therapeutic value for autistic children carrying
MYT1L mutations. We will therefore test throughout all our three aims whether manipulation of these chromatin
factors can rescue the molecular, cellular, or behavioral Myt1l phenotypes.

## Key facts

- **NIH application ID:** 9904331
- **Project number:** 5R01MH115999-02
- **Recipient organization:** STANFORD UNIVERSITY
- **Principal Investigator:** Thomas C. Sudhof
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $734,935
- **Award type:** 5
- **Project period:** 2019-04-01 → 2024-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9904331

## Citation

> US National Institutes of Health, RePORTER application 9904331, The role of Myt1l in the developing and adult mouse brain (5R01MH115999-02). Retrieved via AI Analytics 2026-05-21 from https://api.ai-analytics.org/grant/nih/9904331. Licensed CC0.

---

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