# Role of 14-3-3epsilon in neurite initiation

> **NIH NIH R01** · DREXEL UNIVERSITY · 2020 · $340,161

## Abstract

Project Summary/Abstract
The formation of the intricate neuronal network in the brain requires precise neurogenesis and neuronal
migration followed by neurite and spine formation during development. If neurite and spine formation is
disrupted, it results in a wide range of diseases such as mental illnesses. Recently, patients with a
microduplication of the 17p13.3 chromosome region have been reported and the number of patients exhibiting
this syndrome has been increasing. Interestingly, the patients with this 17p13.3 microduplication syndrome
show severe neurological and morphological defects, including, epilepsy, mental retardation and autism
spectrum disorders (ASD). More interestingly, the studies analyzing this new human genetic syndrome clarified
that the critical region spanning about 70kb is strongly associated with ASD, and this region contains a single
gene, Ywhae, encoding the protein 14-3-3ε. These data strongly suggest that Ywhae might be responsible for
the ASD phenotype in these patients. The functions of 14-3-3ε in neuronal morphogenesis including neurite
formation, have not been previously analyzed and still remain unknown. Therefore, the objectives of this
research proposal are to analyze the novel in vivo functions and molecular targets of 14-3-3ε in neurite
formation, in particular neurite initiation and extension, and clarifying the molecular mechanisms in this cellular
event. We hypothesize that 14-3-3ε plays an important role in neurite initiation as well as neurite extension by
controlling microtubule (MT) sliding and stability through binding to Doublecortin (Dcx) and Microtubule affinity
regulating kinase 3 (Mark3). To test this hypothesis, we propose to use a wide variety of experimental strategies
including in utero electroporation, time-lapse live imaging in vitro and in vivo, tamoxifen-inducible Cre-loxP
system, and 14-3-3ε conditional knockout mice. We have three specific aims. In the Specific Aim 1, we will test
the hypothesis that 14-3-3ε regulates neurite formation and synaptogenesis. In Specific Aim 2, the hypothesis
that 14-3-3ε regulates neurite initiation in the cortex by regulating MT sliding through binding to Dcx will be
tested. In Specific Aim 3, we will test the hypothesis that 14-3-3ε regulates neurite extension by binding to
Mark3 and regulating its activity. The successful completion of this project will not only provide understanding as
to the etiology of a new human genetic syndrome strongly associating with ASD caused by the overexpression
of 14-3-3ε but also significantly enhance our understanding of the precise in vivo functions of 14-3-3ε in neurite
initiation and extension.

## Key facts

- **NIH application ID:** 9991949
- **Project number:** 5R01NS096098-05
- **Recipient organization:** DREXEL UNIVERSITY
- **Principal Investigator:** Kazuhito Toyo-Oka
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $340,161
- **Award type:** 5
- **Project period:** 2016-09-15 → 2023-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9991949

## Citation

> US National Institutes of Health, RePORTER application 9991949, Role of 14-3-3epsilon in neurite initiation (5R01NS096098-05). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/9991949. Licensed CC0.

---

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