Brown N A, McCarthy A, Wolpert L
MRC Experimental Embryology and Teratology Unit, St George's Hospital Medical School, London, UK.
Ciba Found Symp. 1991;162:182-96; discussion 196-201. doi: 10.1002/9780470514160.ch11.
We have proposed a three step model for the specification of left-right in mammalian embryos. The fundamental assumption is that handedness is imparted by an asymmetrical molecule. Conversion of molecular asymmetry to the cellular level gives a property to one side of the embryo to bias an otherwise random generation of an asymmetrical gradient which can be interpreted by developing organs. Rat embryos, treated at discrete stages, show a window of sensitivity for disruption of handedness, which may reflect the time of conversion/biasing. Heat shock and several chemicals cause left-right inversion in up to 50% of embryos exposed during neural groove formation. Earlier stages are less sensitive; no treatment begun after foregut pocket formation influences asymmetry. Evidence for cellular interactions in left-right specification comes from the apparent rescue of iv/iv mutant embryos in chimeras. We are looking for molecular left-right disparity before morphological asymmetry but detect no differences in two-dimensional protein profiles. Using an indirect measure, we find a right-left gradient of tissue oxygen in embryos at the 20-30 somite stage. This may reflect asymmetrical vasculature, as we have suggested to explain drug-induced asymmetrical limb malformations.
我们提出了一个用于确定哺乳动物胚胎左右方向的三步模型。基本假设是，手性是由一种不对称分子赋予的。分子不对称性向细胞水平的转化赋予胚胎一侧一种特性，使其偏向于产生一个原本随机的不对称梯度，而发育中的器官能够解读这个梯度。在离散阶段处理的大鼠胚胎显示出一个对左右方向破坏敏感的窗口期，这可能反映了转化/偏置的时间。热休克和几种化学物质在神经沟形成期间可使高达50%暴露的胚胎出现左右反转。更早的阶段敏感性较低；在前肠囊形成后开始的任何处理都不会影响不对称性。左右方向确定中细胞相互作用的证据来自嵌合体中iv/iv突变胚胎的明显拯救。我们在形态不对称之前寻找分子的左右差异，但在二维蛋白质谱中未检测到差异。使用一种间接测量方法，我们在20 - 30体节阶段的胚胎中发现了组织氧的左右梯度。这可能反映了不对称的血管系统，正如我们为解释药物诱导的不对称肢体畸形所提出的那样。
