Rottbauer Wolfgang, Saurin Andrew J, Lickert Heiko, Shen Xuetong, Burns C Geoff, Wo Z Galen, Kemler Rolf, Kingston Robert, Wu Carl, Fishman Mark
Cardiovascular Research Center, Massachusetts General Hospital and Department of Medicine, Harvard Medical School, Boston, MA 02114, USA.
Cell. 2002 Nov 27;111(5):661-72. doi: 10.1016/s0092-8674(02)01112-1.
Organ size is precisely regulated during development, but the control mechanisms remain obscure. We have isolated a mutation in zebrafish, liebeskummer (lik), which causes development of hyperplastic embryonic hearts. lik encodes Reptin, a component of a DNA-stimulated ATPase complex. The mutation activates ATPase activity of Reptin complexes and causes a cell-autonomous proliferation of cardiomyocytes to begin well after progenitors have fashioned the primitive heart tube. With regard to heart growth, beta-catenin and Pontin, a DNA-stimulated ATPase that is often part of complexes with Reptin, are in the same genetic pathways. Pontin reduction phenocopies the cardiac hyperplasia of the lik mutation. Thus, the Reptin/Pontin ratio serves to regulate heart growth during development, at least in part via the beta-catenin pathway.
器官大小在发育过程中受到精确调控，但其控制机制仍不清楚。我们在斑马鱼中分离出一种名为“liebeskummer（lik）”的突变，它会导致胚胎心脏增生。lik编码Reptin，它是DNA刺激的ATP酶复合物的一个组成部分。该突变激活了Reptin复合物的ATP酶活性，并导致心肌细胞在祖细胞形成原始心管后很久才开始自主增殖。关于心脏生长，β-连环蛋白和Pontin（一种通常与Reptin形成复合物的DNA刺激的ATP酶）处于相同的遗传途径中。Pontin减少模拟了lik突变的心脏增生。因此，Reptin/Pontin的比例至少部分通过β-连环蛋白途径在发育过程中调节心脏生长。
