Department of Biology, University of North Carolina at Chapel Hill, Chapel Hill, NC, United States of America.
PLoS One. 2018 Mar 13;13(3):e0194207. doi: 10.1371/journal.pone.0194207. eCollection 2018.
FOXQ1 is a member of the forkhead-box transcription factor family that has important functions in development, cancer, aging, and many cellular processes. The role of FOXQ1 in cancer biology has raised intense interest, yet much remains poorly understood. We investigated the possible function of the two zebrafish orthologs (foxq1a and foxq1b) of human FOXQ1 in innate immune cell development and function. We employed CRISPR-Cas9 targeted mutagenesis to create null mutations of foxq1a and foxq1b in zebrafish. Using a combination of molecular, cellular, and embryological approaches, we characterized single and double foxq1a bcz11 and foxq1b bcz18 mutants. This study provides the first genetic mutant analyses of zebrafish foxq1a and foxq1b. Interestingly, we found that foxq1a, but not foxq1b, was transcriptionally regulated during a bacterial response, while the expression of foxq1a was detected in sorted macrophages and upregulated in foxq1a-deficient mutants. However, the transcriptional response to E. coli challenge of foxq1a and foxq1b mutants was not significantly different from that of their wildtype control siblings. Our data shows that foxq1a may have a role in modulating bacterial response, while both foxq1a and foxq1b are not required for the development of macrophages, neutrophils, and microglia. Considering the implicated role of FOXQ1 in a vast number of cancers and biological processes, the foxq1a and foxq1b null mutants from this study provide useful genetic models to further investigate FOXQ1 functions.
FOXQ1 是叉头框转录因子家族的成员，在发育、癌症、衰老和许多细胞过程中具有重要功能。FOXQ1 在癌症生物学中的作用引起了极大的兴趣，但仍有许多方面了解甚少。我们研究了人类 FOXQ1 的两个斑马鱼直系同源物（foxq1a 和 foxq1b）在先天免疫细胞发育和功能中的可能作用。我们利用 CRISPR-Cas9 靶向诱变技术在斑马鱼中创建了 foxq1a 和 foxq1b 的缺失突变。我们采用分子、细胞和胚胎学方法相结合，对 foxq1a bcz11 和 foxq1b bcz18 单突变体和双突变体进行了特征描述。这项研究提供了对斑马鱼 foxq1a 和 foxq1b 的首次遗传突变分析。有趣的是，我们发现 foxq1a（而不是 foxq1b）在细菌反应过程中受到转录调控，而 foxq1a 的表达在分选的巨噬细胞中被检测到，并在 foxq1a 缺陷型突变体中上调。然而，foxq1a 和 foxq1b 突变体对大肠杆菌挑战的转录反应与野生型对照兄弟姐妹没有显著差异。我们的数据表明，foxq1a 可能在调节细菌反应中起作用，而 foxq1a 和 foxq1b 都不是巨噬细胞、中性粒细胞和小神经胶质细胞发育所必需的。考虑到 FOXQ1 在大量癌症和生物学过程中的作用，本研究中的 foxq1a 和 foxq1b 缺失突变体为进一步研究 FOXQ1 功能提供了有用的遗传模型。
