Lee K H, Xu Q, Breitbart R E
Department of Cardiology, Children's Hospital, Harvard Medical School, 300 Longwood Avenue, Boston, Massachusetts, 02115, USA.
Dev Biol. 1996 Dec 15;180(2):722-31. doi: 10.1006/dbio.1996.0341.
The Drosophila homeobox gene tinman and its vertebrate homologs Nkx-2.5 and Nkx-2.3 are critical determinants of cardiac development. We report here the identification of a new tinman-related gene, nkx2.7, as well as orthologs of Nkx-2.5 and Nkx-2.3 in the zebrafish. Analysis of their expression in the developing zebrafish embryo reveals that nkx2.7 transcripts are the first to appear in cardiac mesodermal and pharyngeal endodermal precursors of the anterior hypoblast, anticipating both temporally and spatially the later expression of nkx2.5 and nkx2.3 in these lineages. The preeminence of nkx2.7 in these embryonic lineages is consistent with a key role in cell fate determination, perhaps in part through the induction of nkx2.5 and nkx2.3. The findings provide the first molecular clues as to the spatial organization of endodermal and cardiac mesodermal precursors in the zebrafish hypoblast immediately following gastrulation. They suggest a coordinate role for these three tinman-related genes in the development of the heart and pharyngeal arches, and reinforce the paradigm of gene duplication and subspecialization between Drosophila and vertebrate species. The results provide a framework in which to analyze potential changes in tinman-related gene expression during abnormal zebrafish development.
果蝇同源异型框基因tinman及其脊椎动物同源基因Nkx - 2.5和Nkx - 2.3是心脏发育的关键决定因素。我们在此报告鉴定出一个新的tinman相关基因nkx2.7,以及斑马鱼中Nkx - 2.5和Nkx - 2.3的直系同源基因。对它们在斑马鱼胚胎发育过程中的表达分析表明,nkx2.7转录本最早出现在前下胚层的心脏中胚层和咽内胚层前体中,在时间和空间上都先于这些谱系中nkx2.5和nkx2.3的后期表达。nkx2.7在这些胚胎谱系中的优势地位与细胞命运决定中的关键作用一致,可能部分是通过诱导nkx2.5和nkx2.3来实现的。这些发现为原肠胚形成后斑马鱼下胚层中内胚层和心脏中胚层前体的空间组织提供了首个分子线索。它们表明这三个tinman相关基因在心脏和咽弓发育中具有协同作用,并强化了果蝇和脊椎动物物种之间基因复制和亚专业化的模式。这些结果提供了一个框架,用于分析斑马鱼异常发育过程中tinman相关基因表达的潜在变化。