The cell surface membrane proteins cdo and bloc are components and targets of the hedgehog signaling pathway and feedback network in mice
The cell surface membrane proteins cdo and bloc are components and targets of the hedgehog signaling pathway and feedback network in mice
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DOI：
10.1016/j.devcel.2006.04.004
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发表时间：
2006-05-01
影响因子：
11.8
通讯作者：
McMahon, Andrew P.
中科院分区：
文献类型：
--
作者：
Tenzen, Toyoaki;Allen, Benjamin L.;McMahon, Andrew P.
Cdo和Boc编码与肌肉分化相关的细胞表面IG/纤连蛋白超家族成员。这里的数据表明，它们也是Sonic hedgehog（Shh）通路的靶点和信号组分。虽然Cdo和Boc通常由Hedgehog（HH）信号负调控，但在神经管中，Cdo在Shh依赖性底板内表达，而Boc表达位于Shh信号的背侧极限内。Cdo的损失导致地板的Shh剂量依赖性减少。相反，Boc或Cdo的异位表达导致Shh依赖的、细胞自主的腹侧细胞命运的促进和与Shh隔离一致的背侧细胞身份的非细胞自主的腹侧扩张。Cdo和Boc通过与活性所必需的特定纤连蛋白重复的高亲和力相互作用结合Shh。我们提出了一个模型，其中CDO和Boc增强其目标领域内的Shh信号。
Cdo and Boc encode cell surface Ig/fibronectin superfamily members linked to muscle differentiation. Data here indicate they are also targets and signaling components of the Sonic hedgehog (Shh) pathway. Although Cdo and Boc are generally negatively regulated by Hedgehog (HH) signaling, in the neural tube Cdo is expressed within the Shh-dependent floor plate while Boc expression lies within the dorsal limit of Shh signaling. Loss of Cdo results in a Shh dosage-dependent reduction of the floor plate. In contrast, ectopic expression of Boc or Cdo results in a Shh-dependent, cell autonomous promotion of ventral cell fates and a non-cell-autonomous ventral expansion of dorsal cell identities consistent with Shh sequestration. Cdo and Boc bind Shh through a high-affinity interaction with a specific fibronectin repeat that is essential for activity. We propose a model where Cdo and Boc enhance Shh signaling within its target field.