Wu Jinling, Yang Jing, Klein Peter S
Cell and Molecular Biology Graduate Group, University of Pennsylvania School of Medicine, 364 Clinical Research Building, 415 Curie Boulevard, Philadelphia, PA 19104, USA.
Dev Biol. 2005 Mar 1;279(1):220-32. doi: 10.1016/j.ydbio.2004.12.016.
While Wnt signaling is known to be involved in early steps of neural crest development, the mechanism remains unclear. Because Wnt signaling is able to posteriorize anterior neural tissues, neural crest induction by Wnts has been proposed to be an indirect consequence of posteriorization of neural tissues rather than a direct effect of Wnt signaling. To address the relationship between posteriorization and neural crest induction by Wnt signaling, we have used gain of function and loss of function approaches in Xenopus to modulate the level of Wnt signaling at multiple points in the pathway. We find that modulating the level of Wnt signaling allows separation of neural crest induction from the effects of Wnts on anterior-posterior neural patterning. We also find that activation of Wnt signaling induces ectopic neural crest in the anterior region without posteriorizing anterior neural tissues. In addition, Wnt signaling induces neural crest when its posteriorizing activity is blocked by inhibition of FGF signaling in neuralized explants. Finally, depletion of beta-catenin confirms that the canonical Wnt pathway is required for initial neural crest induction. While these observations do not exclude a role for posteriorizing signals in neural crest induction, our data, together with previous observations, strongly suggest that canonical Wnt signaling plays an essential and direct role in neural crest induction.
虽然已知Wnt信号通路参与神经嵴发育的早期步骤，但其机制仍不清楚。由于Wnt信号通路能够使前侧神经组织向后方化，因此有人提出Wnt诱导神经嵴是神经组织向后方化的间接结果，而非Wnt信号通路的直接作用。为了研究Wnt信号通路介导的向后方化与神经嵴诱导之间的关系，我们利用非洲爪蟾的功能获得和功能缺失方法，在该信号通路的多个节点调节Wnt信号水平。我们发现，调节Wnt信号水平可将神经嵴诱导与Wnt对前后神经模式形成的影响区分开来。我们还发现，激活Wnt信号通路会在前侧区域诱导异位神经嵴，而不会使前侧神经组织向后方化。此外，当在神经化外植体中通过抑制FGF信号通路来阻断Wnt信号通路的向后方化活性时，Wnt信号通路仍能诱导神经嵴。最后，β-连环蛋白的缺失证实了经典Wnt信号通路是神经嵴初始诱导所必需的。虽然这些观察结果并不排除向后方化信号在神经嵴诱导中的作用，但我们的数据与之前的观察结果一起，强烈表明经典Wnt信号通路在神经嵴诱导中起重要且直接的作用。
