Robert Benoît, Lallemand Yvan
Department of Developmental Biology, CNRS URA 2578, Pasteur Institute, Paris, France.
Dev Dyn. 2006 Sep;235(9):2337-52. doi: 10.1002/dvdy.20890.
The limb has been a privileged object of investigation and reflection for scientists over the past two centuries and continues to provide a heuristic framework to analyze vertebrate development. Recently, accumulation of new data has significantly changed our view on the mechanisms of limb patterning, in particular along the anterior-posterior axis. These data have led us to revisit the mode of action of the zone of polarizing activity. They shed light on the molecular and cellular mechanisms of patterning linked to the Shh-Gli3 signaling pathway and give insights into the mechanism of activation of these cardinal factors, as well as the consequences of their activity. These new data are in good part the result of systematic Application of tools used in contemporary mouse molecular genetics. These have extended the power of mouse genetics by introducing mutational strategies that allow fine-tuned modulation of gene expression, interchromosomal deletions and duplication. They have even made the mouse embryo amenable to cell lineage analysis that used to be the realm of chick embryos. In this review, we focus on the data acquired over the last five years from the analysis of mouse limb development and discuss new perspectives opened by these results.
在过去的两个世纪里,肢体一直是科学家们进行研究和思考的重点对象,并且持续为分析脊椎动物的发育提供启发式框架。最近,新数据的积累显著改变了我们对肢体模式形成机制的看法,尤其是沿前后轴的机制。这些数据促使我们重新审视极化活性区的作用方式。它们揭示了与Shh-Gli3信号通路相关的模式形成的分子和细胞机制,并深入了解这些关键因子的激活机制及其活性的后果。这些新数据很大程度上是当代小鼠分子遗传学中使用的工具系统应用的结果。通过引入允许对基因表达进行微调的突变策略、染色体间缺失和重复,这些工具扩展了小鼠遗传学的能力。它们甚至使小鼠胚胎能够进行细胞谱系分析,而这曾经是鸡胚胎的研究领域。在这篇综述中,我们重点关注过去五年从对小鼠肢体发育的分析中获得的数据,并讨论这些结果所开启的新视角。