# Musashi1 and miR-137 antagonism: impact on neurogenesis and diseases

> **NIH NIH R21** · UNIVERSITY OF TEXAS HLTH SCIENCE CENTER · 2020 · $424,750

## Abstract

Adult neurogenesis is fundamental to brain function with important roles in memory and repair. During
neurogenesis, dramatic physiological and morphological alterations take place due to coordinated changes in
gene expression driven by specific regulators. Dysregulation can ultimately lead to reduced repair,
neurodegenerative diseases and brain tumor development. We identified a molecular switch between self-renewal and differentiation having as central players Musashi1 and miR-137. These regulators have opposite
expression patterns and functions. Musashi1 (Msi1) is a stem-cell protein implicated in self-renewal while miR-137 functions as a neurogenic miRNA. Msi1 and miR-137 interact at two different levels. First, miR-137 represses
Msi1. Second, genomic analyses revealed that Msi1 and miR-137 regulate in opposite directions a large set of
target genes implicated in cell migration, neuronal differentiation and cell morphogenesis.
 We propose that the balance between Msi1 and miR-137 is a key factor in cell fate decisions. In our
antagonistic model, Msi1 promotes self-renewal mainly by increasing the expression of targets shared with miR-137 while miR-137 drives differentiation using a double negative switch, inhibiting Msi1 and also the their shared
targets.
 In Aim 1, we will use genomic analyses to build an extended regulatory network for Msi1 and miR-137. We
will establish connections (via regulatory, functional or genetic associations) between Msi1/miR-137 shared and
unique targets to other genes displaying changes in expression during neurogenesis and identify other regulators
that potentially function as partners of Msi1 and miR-137. In Aim 2, we will investigate two scenarios relevant to
Alzheimer’s and glioblastoma development: 1) Msi1 inhibition is critical to miR-137 function in differentiation, 2)
if miR-137 high expression is required to maintain the neuronal phenotype and 3) if an increase in Msi1
expression in differentiated cells could trigger cell cycle re-entry and repression of genes that maintain the
neuronal phenotype. Next, to further support our model of antagonism, we will check if inhibition of miR-137
increases Msi1 expression in hippocampal neurons and if the alterations triggered by miR-137 inhibition can be
“neutralized” by silencing Msi1.

## Key facts

- **NIH application ID:** 10064506
- **Project number:** 1R21NS113344-01A1
- **Recipient organization:** UNIVERSITY OF TEXAS HLTH SCIENCE CENTER
- **Principal Investigator:** Erzsebet Kokovay
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $424,750
- **Award type:** 1
- **Project period:** 2020-09-30 → 2024-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10064506

## Citation

> US National Institutes of Health, RePORTER application 10064506, Musashi1 and miR-137 antagonism: impact on neurogenesis and diseases (1R21NS113344-01A1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10064506. Licensed CC0.

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