Yin Ao, Korzh Vladimir, Gong Zhiyuan
Department of Biological Sciences, National University of Singapore, Singapore 117543, Singapore.
Biochim Biophys Acta. 2012 Feb;1823(2):236-44. doi: 10.1016/j.bbamcr.2011.09.018. Epub 2011 Oct 10.
Wnt signaling plays critical roles in development of both tetrapod lung and fish swimbladder, which are the two evolutionary homologous organs. Our previous data reveal that down-regulation of Wnt signaling leads to defective swimbladder development. However, the effects of up-regulation of Wnt signaling on swimbladder development remain unclear. By knockdown of the Wnt protein inhibitory gene wif1, we demonstrated that up-regulation of Wnt signaling also resulted in perturbed development of the swimbladder. Specifically, the growth of epithelium and mesenchyme was greatly inhibited, the smooth muscle differentiation was abolished, and the organization of mesothelium was disturbed. Furthermore, our data reveal that it is the reduced cell proliferation, but not enhanced apoptosis, that contributes to the disturbance of swimbladder development in wif1 morphants. Blocking Wnt signaling by the Wnt antagonist IWR-1 did not affect wif1 expression in the swimbladder, but complete suppression of Hedgehog signaling in smo-/- mutants abolished wif expression, consistent with our earlier report of a negative feedback regulation of Wnt signaling in the swimbladder by the Hedgehog signaling. Our works established the importance of proper level of Wnt signaling for normal development of swimbladder in zebrafish.
Wnt信号通路在四足动物肺和鱼类鳔的发育中起着关键作用，这两个器官是进化上的同源器官。我们之前的数据表明，Wnt信号通路的下调会导致鳔发育缺陷。然而，Wnt信号通路上调对鳔发育的影响仍不清楚。通过敲低Wnt蛋白抑制基因wif1，我们证明Wnt信号通路的上调也会导致鳔发育紊乱。具体而言，上皮和间充质的生长受到极大抑制，平滑肌分化消失，间皮组织紊乱。此外，我们的数据表明，是细胞增殖减少而非凋亡增加导致了wif1 morphants中鳔发育的紊乱。Wnt拮抗剂IWR-1阻断Wnt信号通路并不影响鳔中wif1的表达，但在smo-/-突变体中完全抑制Hedgehog信号通路会消除wif表达，这与我们之前关于Hedgehog信号通路对鳔中Wnt信号通路负反馈调节的报道一致。我们的研究确立了适当水平的Wnt信号通路对斑马鱼鳔正常发育的重要性。
