# Wdr5 and Myc cooperate to regulate formation of neural crest stem cells

## TL;DR

Wdr5 and Myc work together in Xenopus to control the formation of neural crest stem cells, showing the importance of precise protein ratios for cell development.

## Contribution

The study reveals that Wdr5 and Myc interact in a dose- and domain-specific manner to regulate neural crest formation.

## Key findings

- Wdr5 depletion disrupts neural crest gene expression and expands neural plate domains.
- Wdr5 and Myc physically interact and require specific ratios to rescue neural crest formation.
- The WBM and WIN domains of Wdr5 are essential for Myc-dependent gene activation and regulation.

## Abstract

Wdr5, a multifunctional scaffolding protein, with established roles in chromatin regulation and pluripotency, but its functions in early development remain poorly understood. Here, we show that Xenopus wdr5 is expressed in blastula stem cells and enriched in neural crest cells. Depletion of wdr5 abolished neural crest gene expression in embryos and in reprogrammed explants while expanding neural plate border and neural plate domains. Gain-of-function experiments revealed striking dose-dependent effects: low Wdr5 enhanced neural crest formation, whereas high levels suppressed it, suggesting a requirement for precise stoichiometry with interacting partners. We identify Myc as an essential co-factor for Wdr5 in neural crest – Wdr5 and Myc physically interact and co-expression at defined ratios rescues neural crest formation. We further show that the Wdr5 WBM site is required for Myc-dependent activation of neural crest genes, whereas the WIN site regulates myc expression itself; both domains are necessary to rescue wdr5 depletion. These findings reveal that Wdr5 orchestrates neural crest development through multiple, domain-specific mechanisms, integrating stoichiometric control with partner-specific transcriptional regulation, and underscores the importance of precise co-factor ratios in cell fate decisions.

Summary: Wdr5 regulates neural crest development in Xenopus through dose-dependent, domain-specific interactions with Myc, integrating stoichiometric control and transcriptional regulation crucial for balanced cell fate specification.