WD repeat domain 5 (WDR5), which is best known for its role in regulating histone methylation, was recently shown to be mutated in a patient exhibiting congenital heart disease and heterotaxy – a left-right (LR) patterning disorder. Now, Saurabh Kulkarni and Mustafa Khokha investigate this further and reveal that WDR5 regulates ciliogenesis and early LR patterning in Xenopus embryos. They show that morpholino oligo-mediated depletion of Wdr5 alters LR patterning in Xenopus, specifically, expression of the LR patterning markers pitx2c and dand5. They further report that Wdr5 depletion leads to shorter and fewer cilia in the left-right organiser of embryos. Consistent with a role for WDR5 in transcriptional regulation, the expression of foxj1, which encodes a master regulator of ciliogenesis, is reduced in wdr5 morphants. Unexpectedly, the authors discover that a WDR5-GFP fusion protein localises to the base of cilia, and that a chromatin-dead form of WDR5 can partially rescue the LR patterning phenotype of wdr5 morphants, implicating a role for WDR5 independent of its chromatin-modifying activity. Together, these findings reveal that WDR5 plays both chromatin-dependent and –independent roles in LR patterning, and could have important clinical implications for better understanding congenital heart disease and heterotaxy.
