Anderson D J
Division of Biology 216-76, Howard Hughes Medical Institute, California Institute of Technology, Pasadena 91125.
C R Acad Sci III. 1993 Sep;316(9):1082-96.
Avian embryos have traditionally been the system of choice for studying neural crest development, but the combination of reverse genetics and clonal culture should allow new insights to be gained from mammalian systems as well. We describe one of the first examples where a targeted mutation in a developmental control gene, isolated on the basis of its homology to Drosophila neural determination genes, causes a highly selective phenotype affecting the early development of a subset of neural crest derivatives. Detailed analysis of the cellular phenotype and expression pattern of the gene, called MASH-1, have led to novel insights into the genetic logic that controls neural crest development. Most important, some features of the phenotype appear inconsistent with the predictions of current models of neural crest lineage diversification. These unexpected results have forced a reevaluation of our thinking about some aspects of neural crest development, and illustrate the power of the reverse genetic approach to reveal unanticipated features of complex biological systems as well as to suggest new directions for future study.
传统上,鸟类胚胎一直是研究神经嵴发育的首选系统,但反向遗传学和克隆培养相结合,应该也能让我们从哺乳动物系统中获得新的见解。我们描述了首个例子之一,在这个例子中,一个基于与果蝇神经决定基因的同源性而分离出来的发育控制基因发生了靶向突变,导致了一种高度选择性的表型,影响了神经嵴衍生物子集的早期发育。对这个名为MASH-1的基因的细胞表型和表达模式进行详细分析,让我们对控制神经嵴发育的遗传逻辑有了新的认识。最重要的是,该表型的一些特征似乎与当前神经嵴谱系多样化模型的预测不一致。这些意外结果迫使我们重新评估对神经嵴发育某些方面的认识,并说明了反向遗传方法在揭示复杂生物系统未预料到的特征以及为未来研究指明新方向方面的强大作用。