Brown N A, Wolpert L
MRC Experimental Embryology and Teratology Unit, St George's Hospital Medical School, London, UK.
Development. 1990 May;109(1):1-9. doi: 10.1242/dev.109.1.1.
The development of handed asymmetry requires a special mechanism for consistently specifying a difference between left and right sides. This is to be distinguished from both random asymmetry, and from those left/right differences that are mirror symmetrical. We propose a model for the development of handedness in bilateral animals, comprising three components. (i) A process termed conversion, in which a molecular handedness is converted into handedness at the cellular level. A specific model for this process is put forward, based on cell polarity and transport of cellular constituents by a handed molecule. (ii) A mechanism for random generation of asymmetry, which could involve a reaction-diffusion process, so that the concentration of a molecule is higher on one side than the other. The handedness generated by conversion could consistently bias this mechanism to one side. (iii) A tissue-specific interpretation process which responds to the difference between the two sides, and results in the development of different structures on the left and right. There could be direct genetic control of the direction of handedness in this model, most probably through the conversion process. Experimental evidence for the model is considered, particularly the iv mutation in the mouse, which appears to result in loss-of-function in biasing, and so asymmetry is random. The model can explain the abnormal development of handedness observed in bisected embryos of some mammalian, amphibian and sub-vertebrate species. Spiral asymmetry, as seen in spiral cleavage and in ciliates, involves only conversion of molecular asymmetry to the cellular and multicellular level, with no separate interpretation step.
手性不对称的发展需要一种特殊机制，以便始终如一地明确左右两侧的差异。这既不同于随机不对称，也不同于镜像对称的左右差异。我们提出了一个双侧动物手性发展的模型，该模型包含三个组成部分。（i）一个称为转化的过程，其中分子手性在细胞水平上转化为手性。基于细胞极性和手性分子对细胞成分的运输，提出了该过程的一个具体模型。（ii）一种随机产生不对称的机制，这可能涉及反应扩散过程，使得分子浓度在一侧高于另一侧。由转化产生的手性可能会持续地使这种机制偏向一侧。（iii）一种组织特异性的解释过程，它对两侧的差异做出反应，并导致左右两侧发育出不同的结构。在这个模型中，手性方向可能存在直接的遗传控制，最有可能是通过转化过程。考虑了该模型的实验证据，特别是小鼠中的iv突变，它似乎导致了偏向功能的丧失，因此不对称是随机的。该模型可以解释在一些哺乳动物、两栖动物和亚脊椎动物物种的二分胚胎中观察到的手性异常发育。螺旋不对称，如在螺旋卵裂和纤毛虫中所见，仅涉及分子不对称向细胞和多细胞水平的转化，没有单独的解释步骤。
