Small molecule developmental screens reveal the logic and timing of vertebrate development
Small molecule developmental screens reveal the logic and timing of vertebrate development
复制标题
DOI：
10.1073/pnas.97.24.12965
复制
发表时间：
2000-11-21
影响因子：
11.1
通讯作者：
Schreiber, SL
中科院分区：
文献类型：
--
作者：
Peterson, RT;Link, BA;Schreiber, SL
通过随机诱变、随后的表型筛选以及通过靶向基因破坏、随后在模型生物体中进行表型分析，我们已经了解了很多关于脊椎动物发育的知识。由于许多发育事件的发生时间至关重要，因此对基因功能的调节进行时间控制将是有用的，而这对于基因突变体来说通常是不可能的。在这里，我们证明可以通过斑马鱼的发育筛选来鉴定能够进行条件基因产物调节的小分子。我们已经鉴定了几种特异性调节脊椎动物个体发育各个方面的小分子，包括中枢神经系统、心血管系统、神经嵴和耳朵的发育。确定的几种小分子使我们能够剖析黑素细胞和耳石发育的逻辑，并确定这些事件的关键时期。以这种方式鉴定的小分子提供了进一步剖析这些和其他发育过程并鉴定参与脊椎动物发育的新基因的潜力。
Much has been learned about vertebrate development by random mutagenesis followed by phenotypic screening and by targeted gene disruption followed by phenotypic analysis in model organisms. Because the timing of many developmental events is critical, it would be useful to have temporal control over modulation of gene function, a luxury frequently not possible with genetic mutants. Here, we demonstrate that small molecules capable of conditional gene product modulation can be identified through developmental screens in zebrafish, We have identified several small molecules that specifically modulate various aspects of vertebrate ontogeny, including development of the central nervous system, the cardiovascular system, the neural crest, and the ear. Several of the small molecules identified allowed us to dissect the logic of melanocyte and otolith development and to identify critical periods for these events. Small molecules identified in this way offer potential to dissect further these and other developmental processes and to identify novel genes involved in vertebrate development.