Green Julie, Taylor Jennifer J, Hindes Anna, Johnson Stephen L, Goldsmith Matthew I
Department of Pediatrics, Washington University School of Medicine, St. Louis, MO 63110, USA.
Dev Biol. 2009 Oct 1;334(1):224-34. doi: 10.1016/j.ydbio.2009.07.025. Epub 2009 Jul 24.
Mechanisms that regulate the growth and form of the vertebrate skeleton are largely unknown. The zebrafish mutant rapunzel has heterozygous defects in bone development, resulting in skeletal overgrowth, thus identification of the genetic lesion underlying rapunzel might provide insight into the molecular basis of skeletogenesis. In this report, we demonstrate that the rapunzel mutant results from a missense mutation in the previously uncharacterized rpz gene. This conclusion is supported by genetic mapping, identification of a missense mutation in rapunzel(c14) in a highly conserved region of the rpz gene, and suppression of the rapunzel homozygous embryonic phenotype with morpholino knockdown of rpz. In addition, rpz transcripts are identified in regions correlating with the homozygous embryonic phenotype (head, pectoral fin buds, somites and fin fold). This report provides the first gene identification for a mutation affecting segment number in the zebrafish fin and development of both the fin ray (dermal) and the axial skeleton.
调节脊椎动物骨骼生长和形态的机制在很大程度上尚不明确。斑马鱼突变体长发公主在骨骼发育方面存在杂合缺陷，导致骨骼过度生长，因此，确定长发公主突变体潜在的遗传损伤可能会为骨骼发生的分子基础提供见解。在本报告中，我们证明长发公主突变体是由先前未被鉴定的rpz基因中的一个错义突变引起的。这一结论得到了遗传定位、在rpz基因高度保守区域中鉴定出长发公主（c14）中的一个错义突变以及通过rpz的吗啉代敲低对长发公主纯合胚胎表型的抑制的支持。此外，在与纯合胚胎表型相关的区域（头部、胸鳍芽、体节和鳍褶）中鉴定出了rpz转录本。本报告首次鉴定了一个影响斑马鱼鳍节数以及鳍条（真皮）和轴向骨骼发育的突变基因。
