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 which 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 Commd10Tg(Vav1-icre)A2Kio/J mice, where the Vav1-cre transgene is integrated into an intron of the Commd10 gene, creating a functional knockout of Commd10 in homozygous mice. Breeding of heterozygous mice produced no COMMD10-deficient (Commd10Null) offspring, suggesting that COMMD10 is required for embryogenesis. Analysis of Commd10Null embryos demonstrated that they display 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, Commd10Null embryos displayed significantly lower expression levels of a number of transcription factors, including a major regulator of the neural crest, Sox10. Moreover, several cytokines/growth factors involved in early embryonic neurogenesis were also lower in mutant embryos. On the other hand, Commd10Null embryos demonstrated higher expression of genes involved in tissue remodeling and regression processes. Taken together, our findings show that Commd10Null embryos die by day E8.5 due to COMMD10-dependent neural crest failure, revealing a new and critical role of COMMD10 in neural development. RNA-seq analysis of COMMD_Null vs. WT mouse embryo during different stages of embryogenesis: day 8.5 (E8.5), E9.5, and E10.5COMMD家族（含铜代谢MURR1结构域，Copper metabolism MURR1 domain containing）在真核多细胞生物中包含10种结构保守的蛋白（COMMD1至COMMD10），参与众多细胞与生理过程，包括内体运输、铜稳态、胆固醇代谢等。为探究COMMD10在胚胎发育中的功能，本研究使用了Commd10Tg(Vav1-icre)A2Kio/J小鼠，该品系中Vav1-cre转基因整合至Commd10基因的内含子区域，可在纯合子小鼠中实现Commd10的功能性敲除。杂合子小鼠的繁育未获得COMMD10缺陷型（Commd10Null）子代，提示COMMD10是胚胎发生所必需的。对Commd10Null胚胎的分析显示，其发育在胚胎第8.5天（E8.5）时停滞。转录组分析结果表明，突变型胚胎相较于野生型（WT）胚胎，大量神经嵴特异性基因标志物的表达水平显著下调。具体而言，Commd10Null胚胎中多种转录因子的表达水平显著降低，其中包括神经嵴的核心调控因子Sox10。此外，参与早期胚胎神经发生的多种细胞因子/生长因子在突变型胚胎中的表达水平同样下调。与之相反，Commd10Null胚胎中参与组织重塑与退化过程的基因表达水平显著上调。综上，本研究结果表明，Commd10Null胚胎因COMMD10依赖型神经嵴功能异常于E8.5天死亡，揭示了COMMD10在神经发育中全新且关键的作用。本数据集涵盖COMMD缺陷型（COMMD_Null）与野生型（WT）小鼠胚胎在胚胎发育不同阶段（E8.5、E9.5及E10.5）的RNA测序（RNA-seq）分析数据。