PDF(Pubmed)
Abstract：
Integrins are heterodimeric cell surface molecules that mediate cell-extracellular matrix (ECM) adhesion, ECM assembly, and regulation of both ECM and growth factor induced signaling. However, the developmental context of these diverse functions is not clear. Loss of β1-integrin from the lens vesicle (mouse E10.5) results in abnormal exit of anterior lens epithelial cells (LECs) from the cell cycle and their aberrant elongation toward the presumptive cornea by E12.5. These cells lose expression of LEC markers and initiate expression of the Maf (also known as c-Maf) and Prox1 transcription factors as well as other lens fiber cell markers. β1-integrin null LECs also upregulate the ERK, AKT and Smad1/5/8 phosphorylation indicative of BMP and FGF signaling. By E14.5, β1-integrin null lenses have undergone a complete conversion of all lens epithelial cells into fiber cells. These data suggest that shortly after lens vesicle closure, β1-integrin blocks inappropriate differentiation of the lens epithelium into fibers, potentially by inhibiting BMP and/or FGF receptor activation. Thus, β1-integrin has an important role in fine-tuning the response of the early lens to the gradient of growth factors that regulate lens fiber cell differentiation.
摘要：
整合素是介导细胞-细胞外基质（ECM）粘附的异源二聚体细胞表面分子，ECM总成,以及ECM和生长因子诱导的信号传导的调节。然而,这些不同功能的发展背景并不清楚。晶状体囊泡中β1-整合素的丢失（小鼠E10.5）导致前晶状体上皮细胞（LEC）从细胞周期异常退出，并通过E12.5向假定的角膜异常延伸。这些细胞失去LEC标记物的表达并启动Maf(也称为c-Maf)和Prox1转录因子以及其他晶状体纤维细胞标记物的表达。β1-整合素无效LECs也上调ERK，AKT和Smad1/5/8磷酸化指示BMP和FGF信号传导。到E14.5，β1-整合素零晶状体已将所有晶状体上皮细胞完全转化为纤维细胞。这些数据表明晶状体囊泡闭合后不久，β1-整合素阻断晶状体上皮不适当的分化为纤维，可能通过抑制BMP和/或FGF受体激活。因此，β1-整合素在微调早期晶状体对调节晶状体纤维细胞分化的生长因子梯度的反应中具有重要作用。
