COMMD10 Is Essential for Neural Plate Development during Embryogenesis.

The COMMD (copper metabolism MURR1 domain containing) family includes ten structurally conserved proteins (COMMD1 to COMMD10) in eukaryotic multicellular organisms that are involved in a diverse array of cellular and physiological processes, including endosomal trafficking, copper homeostasis, and cholesterol metabolism, among others. To understand the role of COMMD10 in embryonic development, we used /J mice, where the transgene is integrated into an intron of the gene, creating a functional knockout of in homozygous mice. Breeding heterozygous mice produced no COMMD10-deficient offspring, suggesting that COMMD10 is required for embryogenesis. Analysis of embryos demonstrated that they displayed stalled development by embryonic day 8.5 (E8.5). Transcriptome analysis revealed that numerous neural crest-specific gene markers had lower expression in mutant versus wild-type (WT) embryos. Specifically, embryos displayed significantly lower expression levels of a number of transcription factors, including a major regulator of the neural crest, . Moreover, several cytokines/growth factors involved in early embryonic neurogenesis were also lower in mutant embryos. On the other hand, embryos demonstrated higher expression of genes involved in tissue remodeling and regression processes. Taken together, our findings show that embryos die by day E8.5 due to COMMD10-dependent neural crest failure, revealing a new and critical role for COMMD10 in neural development.