Sulf1 influences the Shh morphogen gradient during the dorsal ventral patterning of the neural tube in Xenopus tropicalis.
Sulf1 influences the Shh morphogen gradient during the dorsal ventral patterning of the neural tube in Xenopus tropicalis.
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Sulf1 影响热带爪蟾神经管背腹侧模式形成过程中的 Shh 形态发生素梯度。
DOI：
10.1016/j.ydbio.2014.04.010
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发表时间：
2014
影响因子：
2.7
通讯作者：
Ramsbottom SA
中科院分区：
文献类型：
--
作者：
Ramsbottom SA
遗传研究已经确定硫酸乙酰肝素蛋白聚糖（HSPG）是关键发育调节因子（包括Hedgehog、Wnt/Wg、FGF和BMP/Dpp）信号传导所需的。硫酸乙酰肝素（HS）的合成后重塑被证明可以调节这些相同的信号通路。Sulf 1编码N-乙酰葡糖胺6-O-内硫酸酯酶，这种酶可以特异性地从HS链的高度硫酸化区域的葡糖胺中去除6-O硫酸酯基团。Sulf 1在所有脊椎动物中表达的一个突出方面是它与Sonic hedgehog在神经管底板上的共定位。我们在这里表明，Sulf 1是需要正常规格的神经祖细胞在腹侧神经管，一个过程中已知需要一个梯度的Shh活动。我们在早期Xenopus胚胎中使用单细胞注射编码GFP标记的Shh的mRNA，发现Sulf 1限制配体扩散。此外，我们发现，内源性分布的Shh蛋白在Sulf 1敲低胚胎被改变，其中一个不太陡峭的腹侧到背侧的梯度形式在Sulf 1的情况下，导致更多的扩散分布的Shh。这些数据表明Sulf 1在腹侧神经管中的重要作用，并表明Sulf 1活性通过促进高水平Shh蛋白的腹侧积累来塑造Shh形态梯度的机制。
Genetic studies have established that heparan sulphate proteoglycans (HSPGs) are required for signalling by key developmental regulators, including Hedgehog, Wnt/Wg, FGF, and BMP/Dpp. Post-synthetic remodelling of heparan sulphate (HS) by Sulf1 has been shown to modulate these same signalling pathways.Sulf1codes for an N-acetylglucosamine 6-O-endosulfatase, an enzyme that specifically removes the 6-O sulphate group from glucosamine in highly sulfated regions of HS chains. One striking aspect ofSulf1expression in all vertebrates is its co-localisation with that ofSonic hedgehogin the floor plate of the neural tube. We show here thatSulf1is required for normal specification of neural progenitors in the ventral neural tube, a process known to require a gradient of Shh activity. We use single-cell injection of mRNA coding for GFP-tagged Shh in earlyXenopusembryos and find that Sulf1 restricts ligand diffusion. Moreover, we find that the endogenous distribution of Shh protein in Sulf1 knockdown embryos is altered, where a less steep ventral to dorsal gradient forms in the absence of Sulf1, resulting in more a diffuse distribution of Shh. These data point to an important role for Sulf1 in the ventral neural tube, and suggests a mechanism whereby Sulf1 activity shapes the Shh morphogen gradient by promoting ventral accumulation of high levels of Shh protein.
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影响因子：
11.8
作者：
Tenzen, Toyoaki;Allen, Benjamin L.;McMahon, Andrew P.
通讯作者：
McMahon, Andrew P.
影响因子：
9.8
作者：
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作者：
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25
作者：
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通讯作者：
Segal, Rosalind A.
影响因子：
2.7
作者：
Freeman, Stephen D.;Moore, Wendy M.;Pownall, Mary E.
通讯作者：
Pownall, Mary E.