Terry Fox Laboratory, British Columbia Cancer Agency, Vancouver, British Columbia, Canada V5Z 1L3.
Physiol Genomics. 2010 Feb 4;40(3):150-7. doi: 10.1152/physiolgenomics.00142.2009. Epub 2009 Dec 1.
Valve formation during embryonic heart development involves a complex interplay of regional specification, cell transformations, and remodeling events. While many studies have addressed the role of specific genes during this process, a global understanding of the genetic basis for the regional specification and development of the heart valves is incomplete. We have undertaken genome-wide transcriptional profiling of the developing heart valves in the mouse. Four Serial Analysis of Gene Expression libraries were generated and analyzed from the mouse atrio-ventricular canal (AVC) at embryonic days 9.5-12.5, covering the stages from initiation of endothelial to mesenchymal transition (EMT) through to the beginning of endocardial cushion remodeling. We identified 14 distinct temporal patterns of gene expression during AVC development. These were associated with specific functions and signaling pathway members. We defined the temporal distribution of mesenchyme genes during the EMT process and of specific Notch and transforming growth factor-beta targets. This work provides the first comprehensive temporal dataset during the formation of heart valves. These results identify molecular signatures that distinguish different phases of early heart valve formation allowing gene expression and function to be further investigated.
在胚胎心脏发育过程中，瓣膜的形成涉及到区域特化、细胞转化和重塑事件的复杂相互作用。虽然许多研究已经探讨了特定基因在这个过程中的作用，但对于心脏瓣膜的区域特化和发育的遗传基础还没有全面的了解。我们对小鼠发育中的心脏瓣膜进行了全基因组转录谱分析。从胚胎第 9.5-12.5 天的小鼠房室管（AVC）中生成并分析了四个串联分析基因表达文库，涵盖了从内皮细胞到间充质转化（EMT）的起始阶段，直到心内膜垫重塑的开始。我们在 AVC 发育过程中鉴定了 14 种不同的基因表达时间模式。这些模式与特定的功能和信号通路成员相关。我们定义了 EMT 过程中间质基因的时间分布以及特定的 Notch 和转化生长因子-β靶基因。这项工作提供了心脏瓣膜形成过程中的第一个全面的时间数据集。这些结果确定了区分早期心脏瓣膜形成不同阶段的分子特征，允许进一步研究基因表达和功能。
