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• W2898837899 abstract "Congenital heart disease (CHD) is a major cause of infant mortality and morbidity, yet the genetic causes and mechanisms remain opaque. In a patient with CHD and heterotaxy, a disorder of left-right (LR) patterning, a de novo mutation was identified in the chromatin modifier, WDR5. WDR5 acts as a scaffolding protein in the H3K4 methyltransferase complex, but a role in LR patterning is unknown. Here, we show that Wdr5 depletion leads to LR patterning defects in Xenopus via its role in ciliogenesis. Unexpectedly, we find a dual role for WDR5 in LR patterning. First, WDR5 is expressed in the nuclei of monociliated cells of the LR organizer (LRO) and regulates foxj1 expression. LR defects in wdr5 morphants can be partially rescued with the addition of foxj1. Second, WDR5 localizes to the bases of cilia. Using a mutant form of WDR5, we demonstrate that WDR5 also has an H3K4 independent role in LR patterning. Guided by the patient phenotype, we identify multiple roles for WDR5 in LR patterning, providing plausible mechanisms for its role in ciliopathies like heterotaxy and CHD." @default.
• W2898837899 created "2018-11-09" @default.
• W2898837899 creator A5001139520 @default.
• W2898837899 creator A5067795566 @default.
• W2898837899 date "2018-01-01" @default.
• W2898837899 modified "2023-10-18" @default.
• W2898837899 title "WDR5 regulates left-right patterning via chromatin dependent and independent functions" @default.
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• W2898837899 doi "https://doi.org/10.1242/dev.159889" @default.
• W2898837899 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/6288385" @default.
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• W2898837899 hasPublicationYear "2018" @default.
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