Department of Cell Biology and the Morphogenesis and Regenerative Medicine Institute, University of Virginia Health System, Charlottesville, VA 22908, USA.
Dev Biol. 2012 Mar 1;363(1):147-54. doi: 10.1016/j.ydbio.2011.12.031. Epub 2011 Dec 28.
Pericellular proteolysis by ADAM family metalloproteinases has been widely implicated in cell signaling and development. We recently found that Xenopus ADAM13, an ADAM metalloproteinase, is required for activation of canonical Wnt signaling during cranial neural crest (CNC) induction by regulating a novel crosstalk between Wnt and ephrin B (EfnB) signaling pathways (Wei et al., 2010b). In the present study we show that the metalloproteinase activity of ADAM13 also plays important roles in eye development in Xenopus tropicalis. Knockdown of ADAM13 results in reduced expression of eye field markers pax6 and rx1, as well as that of the pan-neural marker sox2. Activation of canonical Wnt signaling or inhibition of forward EfnB signaling rescues the eye defects caused by loss of ADAM13, suggesting that ADAM13 functions through regulation of the EfnB-Wnt pathway interaction. Downstream of Wnt, the head inducer Cerberus was identified as an effector that mediates ADAM13 function in early eye field formation. Furthermore, ectopic expression of the Wnt target gene snail2 restores cerberus expression and rescues the eye defects caused by ADAM13 knockdown. Together these data suggest an important role of ADAM13-regulated Wnt activity in eye development in Xenopus.
ADAM 家族金属蛋白酶对细胞周围的蛋白进行水解，在细胞信号转导和发育过程中起着广泛的作用。我们最近发现，非洲爪蟾 ADAM13（一种 ADAM 金属蛋白酶）通过调节 Wnt 和 Ephrin B（EfnB）信号通路之间的新的串扰，在颅神经嵴（CNC）诱导过程中激活经典 Wnt 信号通路中是必需的（Wei 等人，2010b）。在本研究中，我们表明 ADAM13 的金属蛋白酶活性在非洲爪蟾的眼睛发育中也起着重要作用。ADAM13 的敲低导致眼域标记物 pax6 和 rx1 以及泛神经标记物 sox2 的表达减少。经典 Wnt 信号的激活或 EfnB 信号的抑制可挽救 ADAM13 缺失引起的眼睛缺陷，表明 ADAM13 通过调节 EfnB-Wnt 途径的相互作用起作用。在 Wnt 的下游，头部诱导因子 Cerberus 被鉴定为介导 ADAM13 在早期眼域形成中的作用的效应物。此外，Wnt 靶基因 snail2 的异位表达恢复了 cerberus 的表达，并挽救了 ADAM13 敲低引起的眼睛缺陷。这些数据共同表明 ADAM13 调节的 Wnt 活性在非洲爪蟾眼睛发育中起着重要作用。
