Kelley Melissa, Yochem John, Krieg Michael, Calixto Andrea, Heiman Maxwell G, Kuzmanov Aleksandra, Meli Vijaykumar, Chalfie Martin, Goodman Miriam B, Shaham Shai, Frand Alison, Fay David S
Department of Molecular Biology, University of Wyoming, Laramie, United States.
Department of Molecular and Cellular Physiology, Stanford University, Stanford, United States.
Elife. 2015 Mar 23;4:e06565. doi: 10.7554/eLife.06565.
During development, biomechanical forces contour the body and provide shape to internal organs. Using genetic and molecular approaches in combination with a FRET-based tension sensor, we characterized a pulling force exerted by the elongating pharynx (foregut) on the anterior epidermis during C. elegans embryogenesis. Resistance of the epidermis to this force and to actomyosin-based circumferential constricting forces is mediated by FBN-1, a ZP domain protein related to vertebrate fibrillins. fbn-1 was required specifically within the epidermis and FBN-1 was expressed in epidermal cells and secreted to the apical surface as a putative component of the embryonic sheath. Tiling array studies indicated that fbn-1 mRNA processing requires the conserved alternative splicing factor MEC-8/RBPMS. The conserved SYM-3/FAM102A and SYM-4/WDR44 proteins, which are linked to protein trafficking, function as additional components of this network. Our studies demonstrate the importance of the apical extracellular matrix in preventing mechanical deformation of the epidermis during development.
在发育过程中,生物力学力塑造身体轮廓并为内部器官赋予形状。我们结合遗传和分子方法以及基于荧光共振能量转移(FRET)的张力传感器,对秀丽隐杆线虫胚胎发育期间伸长的咽部(前肠)对表皮前部施加的拉力进行了表征。表皮对这种力以及基于肌动球蛋白的周向收缩力的抵抗是由FBN-1介导的,FBN-1是一种与脊椎动物原纤蛋白相关的ZP结构域蛋白。fbn-1在表皮内具有特异性需求,FBN-1在表皮细胞中表达并作为胚胎鞘的假定成分分泌到顶端表面。基因芯片研究表明,fbn-1 mRNA加工需要保守的可变剪接因子MEC-8/RBPMS。与蛋白质运输相关的保守蛋白SYM-3/FAM102A和SYM-4/WDR44作为该网络的其他成分发挥作用。我们的研究证明了顶端细胞外基质在发育过程中防止表皮机械变形的重要性。