Essential roles of DCAF7/WDR68 in mouse embryonic development.

BACKGROUND: DCAF7/WDR68 (hereafter WDR68) is a highly conserved WD40 repeat protein across species and its role in mouse embryonic development is still unknown. METHODS: The mice deficient in WDR68 function by gene targeting were generated for its functional research. Several single-cell RNA-sequencing datasets that collectively span mouse gastrulation and organogenesis were integrated for reconstruction of expression trajectory of WDR68 spanning mouse embryogenesis. Weighted gene co-expression network analysis (WGCNA) was used for functional enrichment of co-expression genes of WDR68 in early embryos. Whole-embryo transcriptomic analyses were employed to reveal differentially expressed genes in WDR68-knockout mouse embryos. Co-immunoprecipitation in combination with liquid chromatography-mass spectrometry analysis was performed to examine the interacting proteins of WDR68. RESULTS: WDR68 null mutants exhibited intrauterine growth retardation (IUGR) and died during gestation. Mechanistically, WDR68 deficiency resulted in deregulated expression of development-related genes and activated Hypoxia-inducible factor-1 (HIF-1) pathway. The interactomics confirmed that WDR68 interacts with development-related proteins including AUTS2 and PCGF5. CONCLUSIONS: WDR68 is required for mouse embryonic development and may be a potential target for prevention and treatment of intrauterine growth retardation in the future. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12967-025-06639-4.