foxc1 is required for embryonic head vascular smooth muscle differentiation in zebrafish.
foxc1 is required for embryonic head vascular smooth muscle differentiation in zebrafish.
复制标题
DOI：
10.1016/j.ydbio.2019.06.005
复制
发表时间：
2019-09
影响因子：
2.7
通讯作者：
Thomas R. Whitesell;Paul W Chrystal;J. Ryu;N. Munsie;A. Grosse;Curtis R. French;M. Workentine;
中科院分区：
文献类型：
--
作者：
Thomas R. Whitesell;Paul W Chrystal;J. Ryu;N. Munsie;A. Grosse;Curtis R. French;M. Workentine;
头部血管平滑肌起源于神经嵴，但vSMC谱系的发育机制和早期转录驱动因素尚不清楚。我们发现在发育早期，转录因子foxc1bis在与血管内皮相关的间充质细胞中表达。利用延时成像技术，我们观察到表达foxc1的间充质细胞分化为表达acta2的血管壁细胞。我们发现，在斑马鱼中，虽然efoxc1bis在与大直径血管相关的inacta2阳性平滑肌细胞中共表达，但在epdgfrβ阳性周细胞所在的毛细血管中不共表达。除了作为谱系的早期标记外，foxc1对vSMC分化至关重要；我们发现foxc1功能缺失突变体有缺陷的vSMC分化，表达foxc1的人群的早期基因消融阻断了vSMC的分化。此外，foxc1在facta2的上游表达，是vsmc中acta2表达所必需的。使用RNA-Seq，我们确定了一个富集的交叉基因表达谱，使用双表达的oxc1bandacta2来鉴定新的vSMC标记。综上所述，我们的数据表明foxc1是vSMCs的标记物，在促进其分化中起着关键的功能作用。
Vascular smooth muscle of the head derives from neural crest, but developmental mechanisms and early transcriptional drivers of the vSMC lineage are not well characterized. We find that in early development, the transcription factorfoxc1bis expressed in mesenchymal cells that associate with the vascular endothelium. Using timelapse imaging, we observe thatfoxc1bexpressing mesenchymal cells differentiate intoacta2expressing vascular mural cells. We show that in zebrafish, whilefoxc1bis co-expressed inacta2positive smooth muscle cells that associate with large diameter vessels, it is not co-expressed in capillaries wherepdgfrβpositive pericytes are located. In addition to being an early marker of the lineage,foxc1is essential for vSMC differentiation; we find thatfoxc1loss of function mutants have defective vSMC differentiation and that early genetic ablation offoxc1boracta2expressing populations blocks vSMC differentiation. Furthermore,foxc1is expressed upstream ofacta2and is required foracta2expression in vSMCs. Using RNA-Seq we determine an enriched intersectional gene expression profile using dual expression offoxc1bandacta2to identify novel vSMC markers. Taken together, our data suggests thatfoxc1is a marker of vSMCs and plays a critical functional role in promoting their differentiation.