Papageorgiou S
N.R.C. Demokritos, Athens, Greece.
J Theor Biol. 1998 May 7;192(1):43-53.
A mechanism was recently proposed which controls the expression of Hoxa genes in the developing vertebrate limb. This is a three-dimensional diffusion model of a morphogen Ma secreted at the apical ectodermal ridge. The morphogen Ma is at the same time degraded by first order chemical kinetics. The emerging diffusion gradient, supplemented with a natural sequence of thresholds, can explain the spatial and temporal collinearities of the Hoxa gene expression domains. In the present model it is assumed that a second diffusing morphogen Mz is produced at the zone of polarizing activity. A concentration superposition of morphogens Ma and Mz can then explain the observed pattern of expression of Hoxd-10, 11, 12, and 13 during normal limb development (spatial and temporal collinearity). The associated thresholds for gene expression increase sequentially from Hoxd-10 to Hoxd-13 (threshold collinearity). The observed deformations or deletions of these expression domains in manipulated limbs are also explained by the model. Additional model predictions are proposed to test the validity of the model. In patterning two mechanisms are mainly considered as responsible for signalling: (i) a gradient of a long-range morphogen created by passive diffusion; and (ii) a short-range inducer initiating a cascade of consecutive signals. A time-test is proposed which distinguishes the modes of specific gene expressions for these distinct signalling mechanisms.
最近提出了一种机制，该机制控制发育中的脊椎动物肢体中Hoxa基因的表达。这是一种在顶端外胚层嵴分泌的形态发生素Ma的三维扩散模型。形态发生素Ma同时通过一级化学动力学降解。出现的扩散梯度，辅以自然的阈值序列，可以解释Hoxa基因表达域的空间和时间共线性。在当前模型中，假设在极化活性区产生第二种扩散形态发生素Mz。形态发生素Ma和Mz的浓度叠加然后可以解释在正常肢体发育期间观察到的Hoxd-10、11、12和13的表达模式（空间和时间共线性）。基因表达的相关阈值从Hoxd-10到Hoxd-13依次增加（阈值共线性）。该模型还解释了在操作肢体中观察到的这些表达域的变形或缺失。提出了额外的模型预测以测试该模型的有效性。在模式形成中，主要考虑两种负责信号传导的机制：(i) 通过被动扩散产生的长程形态发生素的梯度；以及(ii) 启动连续信号级联的短程诱导剂。提出了一种时间测试，以区分这些不同信号传导机制的特定基因表达模式。
