Balancing Hedgehog, a retention and release equilibrium given by Dally, Ihog, Boi and shifted/DmWif

Balancing Hedgehog, a retention and release equilibrium given by Dally, Ihog, Boi and shifted/DmWif
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DOI:
10.1016/j.ydbio.2012.12.013
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发表时间:
2013-04-15
影响因子:
2.7
通讯作者:
Guerrero, Isabel
Guerrero, Isabel
中科院分区:
生物学3区
文献类型:
--
作者:
Bilioni, Aphrodite;Sanchez-Hernandez, David;Guerrero, Isabel

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Hedgehog可以在短距离和长距离上发出信号,并在各种系统的发育过程中充当形态发生剂。我们研究了Hh的释放和传播的机制,果蝇翅成虫盘作为极化上皮的模型系统。我们分析了磷脂酰肌醇蛋白聚糖Dally,细胞外因子移位(Shf,也称为DmWif),免疫球蛋白样(Ig样)和纤连蛋白III(FNNIII)结构域包含跨膜蛋白,干扰刺猬(Ihog)及其相关蛋白Ihog兄弟(Boi)的合作作用,在Hh的稳定性,释放和传播。我们发现,达利和博伊是必要的,以防止顶端分散的Hh,他们也有助于Hh回收其释放沿着基底外侧部分的上皮形成一个长距离的梯度。另一方面,Shf/DmWif促进由Ihog、Boi和Dally限制的Hh运动,在膜附着和Hh释放之间建立平衡。此外,这种蛋白质复合物是薄的丝状伪足样结构或细胞丝的一部分,这表明Dally,Ihog,Boi和Shf/DmWif之间的相互作用是梯度形成过程中细胞丝介导的Hh分布所必需的。(C)2013 Elsevier Inc. All rights reserved.
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. (C) 2013 Elsevier Inc. All rights reserved.