# An In Vivo Drug Screen Reveals That Sirtuin 2 Activity Promotes Spinal Cord Neurogenesis in Developing Zebrafish

## TL;DR

This study finds that SIRT2 promotes spinal cord neuron development in zebrafish, suggesting it could be a target for spinal cord repair.

## Contribution

The study reveals a new role for SIRT2 in promoting spinal cord neurogenesis through regulating progenitor cell mitotic activity.

## Key findings

- SIRT2 activity promotes the generation of serotonergic interneurons in the spinal cord.
- Inhibiting SIRT2 reduces serotonergic neuron production and causes locomotor deficits.
- SIRT2 regulates mitotic activity in progenitor cells during spinal cord development.

## Abstract

Given the central role of neurogenesis in building a functional nervous system, we recently developed a zebrafish-based drug-screening protocol to uncover molecules and signalling pathways regulating spinal cord neurogenesis. In this study, we have expanded this drug screen and discovered a previously unknown role of deacetylase sirtuin 2 (SIRT2) in promoting the generation of serotonergic interneurons in the spinal cord. Treatments with specific SIRT2 inhibitors reduced the generation of serotonergic neurons in the spinal cord, which led to locomotor deficits. Our data suggest that SIRT2 regulates mitotic activity in progenitor cells to promote the generation of serotonergic neurons in developing animals. Together, our results uncover SIRT2 as a key regulator of spinal cord neurogenesis and position it as a promising target for strategies aimed at neural repair in spinal cord disorders.