LaGamba Damian, Nawshad Ali, Hay Elizabeth D
Department of Cell Biology, Harvard Medical School, Boston, MA 02115, USA.
Dev Dyn. 2005 Sep;234(1):132-42. doi: 10.1002/dvdy.20489.
One of the most fundamental biological processes in development, as well as a primary mechanism for tumor metastasis, is epithelial-mesenchymal transformation (EMT). To gain a greater understanding of this transition, we have obtained a genomic profile of the critical stages before and during this rapid change in morphology in the developing mouse palate. By isolating the medial edge epithelium of each palatal shelf, we were able to obtain pure gene expression data without contamination from surrounding mesenchymal cells. Our results support the important role of the TGF-beta/Smad signal transduction pathway in the stimulation of EMT by means of up-regulation of the EMT-inducing gene, LEF-1. We document changes in gene expression profiles during palatal adherence and subsequent transformation of the medial edge epithelial seam that suggests a high number of LEF-1 target genes promote cellular transformation to mesenchyme. These include genes involved in cell adhesion, polarity, cytoskeletal dynamics, migration, and intracellular signaling. This knowledge of the changes in gene expression levels during palatogenesis should lead to a better understanding of the mechanisms of EMT.
上皮-间质转化(EMT)是发育过程中最基本的生物学过程之一,也是肿瘤转移的主要机制。为了更深入地了解这种转变,我们获得了发育中小鼠腭部形态快速变化之前和期间关键阶段的基因组图谱。通过分离每个腭突的内侧边缘上皮,我们能够获得纯净的基因表达数据,而不会受到周围间充质细胞的污染。我们的结果支持TGF-β/Smad信号转导通路通过上调EMT诱导基因LEF-1在刺激EMT中发挥的重要作用。我们记录了腭部黏附过程中以及随后内侧边缘上皮缝转化过程中的基因表达谱变化,这表明大量LEF-1靶基因促进细胞向间充质转化。这些基因包括参与细胞黏附、极性、细胞骨架动力学、迁移和细胞内信号传导的基因。对腭形成过程中基因表达水平变化的了解应有助于更好地理解EMT的机制。