Papageorgiou Spyros
Institute of Biology, NRC Demokritos Aghia Paraskevi Attikis, Athens, Greece.
Bioessays. 2004 Feb;26(2):189-95. doi: 10.1002/bies.10387.
A model is proposed that deals with the observed collinearities (spatial, temporal and quantitative) of Hox gene expression during pattern formation along the primary and secondary axes of vertebrates. In particular, in the proximodistal axis of the developing limb, it is assumed that a morphogen gradient is laid down with its source at the distal tip of the bud. The extracellular signals in every cell of the morphogenetic field are transduced and uniformly amplified so that molecules are produced in the nucleus with appropriate physicochemical properties. These molecules can exert a concentration-dependent force on the Hox cluster. It is assumed that, before activation, the Hox cluster is packaged as an elongated rigid body inside the chromatin and is covered by a coat that prevents the transcription factors reaching the genes of the cluster. The transcription factors are confined to the interchromatin domain and their density decreases with their distance from the chromatin surface. A gradual increase in the extracellular morphogen concentration causes a corresponding increase in the number of the nuclear molecules and the resulting bigger force pushes the Hox cluster toward the interchromatin domain. The step-by-step translocations of the Hox cluster initiate the consecutive exposure of genes to their transcription factors. The model explains how gene activation is triggered and it describes spatial, temporal and quantitative collinearities at the initial stages of gene expression. Some recent experiments of Hox deletions and duplications are accounted for by the model.
本文提出了一个模型，用于处理脊椎动物沿主轴和次轴模式形成过程中观察到的Hox基因表达的共线性（空间、时间和定量）。特别是，在发育肢体的近远轴上，假定形态发生素梯度从芽的远端开始形成。形态发生场中每个细胞的细胞外信号被转导并均匀放大，从而在细胞核中产生具有适当物理化学性质的分子。这些分子可以对Hox基因簇施加浓度依赖性力。假定在激活之前，Hox基因簇作为一个细长的刚体包装在染色质内部，并被一层阻止转录因子到达基因簇基因的外壳覆盖。转录因子被限制在染色质间结构域，其密度随着与染色质表面距离的增加而降低。细胞外形态发生素浓度的逐渐增加导致核分子数量相应增加，由此产生的更大的力将Hox基因簇推向染色质间结构域。Hox基因簇的逐步易位启动了基因对其转录因子的连续暴露。该模型解释了基因激活是如何触发，并描述了基因表达初始阶段的空间、时间和定量共线性。最近一些Hox基因缺失和重复的实验也可以用该模型来解释。
