# Vestigial-like 4 Regulates Neurogenesis and Neural Crest Formation During Xenopus Development

## TL;DR

This study shows that Vestigial-like 4 is essential for neurogenesis and neural crest formation in Xenopus embryos, independent of its interaction with TEAD proteins.

## Contribution

The study reveals a novel role of Vestigial-like 4 in early vertebrate development beyond its known interaction with TEADs.

## Key findings

- Vestigial-like 4 is crucial for neurogenesis and neural crest formation in Xenopus.
- Neurog1 and Neurod1 cannot stimulate neurogenesis in embryos lacking Vestigial-like 4.
- Vestigial-like 4 regulates neural crest formation via Pax3 and Sox9, independent of TEAD interaction.

## Abstract

VESTIGIAL-LIKE proteins constitute a family of evolutionarily conserved proteins that act as cofactors in regulating gene expression through their binding to TEAD transcription factors. Among the four members of this family in vertebrates, VESTIGIAL-LIKE 4 has emerged as a tumor suppressor that competes with YAP in binding TEADs, thus inhibiting the HIPPO pathway downstream of YAP. Nevertheless, very few studies have addressed its function during early vertebrate development. Here, we used gain- and loss-of-function strategies to investigate the role of vestigial-like 4 during Xenopus laevis development. Our data show that vestigial-like 4 is a key regulator of neurogenesis and neural crest formation. In embryos depleted of vestigial-like 4, neurogenesis is severely impaired, and neither neurog1 nor neurod1 is able to stimulate neurogenesis. Vestigial-like 4 is also required for neural crest formation through pax3 and sox9 regulation, and this property does not necessarily require its interaction with tead. Collectively, our findings demonstrate that vestigial-like 4 is an important regulator of neurogenesis and neural crest formation. Although vestigial-like 4 can bind to tead proteins in the embryo, its function does not depend solely on this interaction, suggesting a complex level of regulation with which vestigial-like 4 regulates early steps in development and differentiation.