Pathania Mallika, Wang Yan, Simirskii Vladimir N, Duncan Melinda K
Department of Biological Sciences, University of Delaware, Newark, DE 19716, USA.
Department of Biological Sciences, University of Delaware, Newark, DE 19716, USA.
Differentiation. 2016 Oct-Nov;92(4):133-147. doi: 10.1016/j.diff.2016.08.002. Epub 2016 Sep 3.
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.
整合素是异二聚体细胞表面分子，介导细胞与细胞外基质（ECM）的黏附、ECM组装以及ECM和生长因子诱导信号的调节。然而，这些多样功能的发育背景尚不清楚。晶状体泡（小鼠胚胎第10.5天）中β1整合素的缺失导致前晶状体上皮细胞（LEC）异常退出细胞周期，并在胚胎第12.5天时向假定的角膜方向异常伸长。这些细胞失去LEC标志物的表达，并开始表达Maf（也称为c-Maf）和Prox1转录因子以及其他晶状体纤维细胞标志物。β1整合素缺失的LEC还上调了ERK、AKT以及Smad1/5/8的磷酸化，这表明存在骨形态发生蛋白（BMP）和成纤维细胞生长因子（FGF）信号。到胚胎第14.5天时，β1整合素缺失的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，在晶状体泡闭合后不久，β1整合素可能通过抑制BMP和/或FGF受体激活，阻止晶状体上皮细胞不适当分化为纤维细胞。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起重要作用。
