Department of Molecular Biosciences and Robert H. Lurie Comprehensive Cancer Center, Northwestern University, Evanston, Illinois 60208, USA.
Nat Cell Biol. 2012 Mar 25;14(5):518-25. doi: 10.1038/ncb2467.
Networks of epithelial and endothelial tubes are essential for the function of organs such as the lung, kidney and vascular system. The sizes and shapes of these tubes are highly regulated to match their individual functions. Defects in tube size can cause debilitating diseases such as polycystic kidney disease and ischaemia. It is therefore critical to understand how tube dimensions are regulated. Here we identify the tyrosine kinase Src as an instructive regulator of epithelial-tube length in the Drosophila tracheal system. Loss-of-function Src42 mutations shorten tracheal tubes, whereas Src42 overexpression elongates them. Surprisingly, Src42 acts distinctly from known tube-size pathways and regulates both the amount of apical surface growth and, with the conserved formin dDaam, the direction of growth. Quantitative three-dimensional image analysis reveals that Src42- and dDaam-mutant tracheal cells expand more in the circumferential than the axial dimension, resulting in tubes that are shorter in length-but larger in diameter-than wild-type tubes. Thus, Src42 and dDaam control tube dimensions by regulating the direction of anisotropic growth, a mechanism that has not previously been described.
上皮细胞和内皮细胞管的网络对于肺、肾和脉管系统等器官的功能至关重要。这些管的大小和形状受到高度调节以匹配其各自的功能。管大小的缺陷可导致如多囊肾病和缺血等使人虚弱的疾病。因此，了解管尺寸如何受到调节至关重要。在这里，我们鉴定出酪氨酸激酶Src 是果蝇气管系统中上皮管长度的一个有指导意义的调节因子。功能丧失的 Src42 突变使气管管缩短，而 Src42 过表达则使气管管延长。令人惊讶的是，Src42 与已知的管尺寸途径明显不同，它调节顶端表面生长的量，以及与保守的formin dDaam 一起，调节生长的方向。定量三维图像分析显示，Src42 和 dDaam 突变的气管细胞在圆周方向上比在轴向方向上扩张得更多，导致气管管比野生型气管管更短，但直径更大。因此，Src42 和 dDaam 通过调节各向异性生长的方向来控制管尺寸，这是一种以前未被描述的机制。
