Chen J N, van Eeden F J, Warren K S, Chin A, Nüsslein-Volhard C, Haffter P, Fishman M C
Cardiovascular Research Center, Massachusetts General Hospital, Charlestown 02129, USA.
Development. 1997 Nov;124(21):4373-82. doi: 10.1242/dev.124.21.4373.
The first evident break in left-right symmetry of the primitive zebrafish heart tube is the shift in pattern of BMP4 expression from radially symmetric to left-predominant. The midline heart tube then 'jogs' to the left and subsequently loops to the right. We examined 279 mutations, affecting more than 200 genes, and found 21 mutations that perturb this process. Some cause BMP4 to remain radially symmetric. Others randomize the asymmetric BMP4 pattern. Retention of BMP4 symmetry is associated with failure to jog: right-predominance of the BMP4 pattern is associated with reversal of the direction of jogging and looping. Raising BMP4 diffusely throughout the heart, via sonic hedgehog injection, or the blocking of its action by injection of a dominant negative BMP4 receptor, prevent directional jogging or looping. The genes crucial to directing cardiac asymmetry include a subset of those needed for patterning the dorsoventral axis and for notochord and ventral spinal cord development. Thus, the pattern of cardiac BMP4 appears to be in the pathway by which the heart interprets lateralizing signals from the midline.
原始斑马鱼心脏管左右对称性的首次明显破坏是骨形态发生蛋白4（BMP4）表达模式从径向对称转变为左侧占主导。然后，中线心脏管“向左弯曲”，随后向右环化。我们研究了279个影响200多个基因的突变，发现21个突变扰乱了这一过程。一些突变导致BMP4保持径向对称。其他突变则使不对称的BMP4模式随机化。BMP4对称性的保留与无法向左弯曲有关：BMP4模式右侧占主导与弯曲和环化方向的逆转有关。通过注射音猬因子在整个心脏中广泛提高BMP4水平，或通过注射显性负性BMP4受体阻断其作用，会阻止定向弯曲或环化。指导心脏不对称性的关键基因包括那些在背腹轴模式形成以及脊索和腹侧脊髓发育中所需基因的一个子集。因此，心脏BMP4的模式似乎处于心脏解释来自中线的侧化信号的途径中。
