Centro de Biología Molecular "Severo Ochoa" (CSIC-UAM), C/Nicolas Cabrera 1, Universidad Autónoma de Madrid, Cantoblanco, E-28049 Madrid, Spain.
Dev Biol. 2013 Apr 15;376(2):198-212. doi: 10.1016/j.ydbio.2012.12.013. Epub 2012 Dec 29.
Hedgehog can signal both at a short and long-range, and acts as a morphogen during development in various systems. We studied the mechanisms of Hh release and spread using the Drosophila wing imaginal disc as a model system for polarized epithelium. We analyzed the cooperative role of the glypican Dally, the extracellular factor Shifted (Shf, also known as DmWif), and the Immunoglobulin-like (Ig-like) and Fibronectin III (FNNIII) domain-containing transmembrane proteins, Interference hedgehog (Ihog) and its related protein Brother of Ihog (Boi), in the stability, release and spread of Hh. We show that Dally and Boi are required to prevent apical dispersion of Hh; they also aid Hh recycling for its release along the basolateral part of the epithelium to form a long-range gradient. Shf/DmWif on the other hand facilitates Hh movement restrained by Ihog, Boi and Dally, establishing equilibrium between membrane attachment and release of Hh. Furthermore, this protein complex is part of thin filopodia-like structures or cytonemes, suggesting that the interaction between Dally, Ihog, Boi and Shf/DmWif is required for cytoneme-mediated Hh distribution during gradient formation.
刺猬可以在短距离和长距离进行信号传递，并在各种系统的发育过程中充当形态发生素。我们使用果蝇翅膀的胚胎盘作为极化上皮的模型系统，研究了 Hh 释放和扩散的机制。我们分析了糖蛋白 Dally、细胞外因子 Shifted（Shf，也称为 DmWif）以及包含免疫球蛋白样（Ig 样）和纤维连接蛋白 III（FNNIII）结构域的跨膜蛋白干扰刺猬（Ihog）及其相关蛋白 Brother of Ihog（Boi）在 Hh 的稳定性、释放和扩散中的协同作用。我们表明，Dally 和 Boi 是防止 Hh 顶端分散所必需的；它们还帮助 Hh 进行再循环，以便沿上皮的基底外侧部分释放，从而形成长距离梯度。另一方面，Shf/DmWif 促进了受 Ihog、Boi 和 Dally 限制的 Hh 运动，在 Hh 的膜附着和释放之间建立了平衡。此外，该蛋白质复合物是薄丝状伪足样结构或纤毛的一部分，这表明 Dally、Ihog、Boi 和 Shf/DmWif 之间的相互作用对于纤毛介导的梯度形成过程中的 Hh 分布是必需的。
