2012年9月12日 讯 /生物谷BIOON/ --来自美国犹他大学的研究人员对调节下丘脑中成体神经细胞再生方面获得新的深入认识。根据9月12日刊登在Developmental Cell期刊上的一篇论文,他们报道,一种被称作Wnt信号通路的细胞间通信网络在下丘脑中神经前体细胞产生和特化中发挥着重要作用。
论文通信作者Richard Dorsky博士说,“在我们早期的研究中,我们发现Wnt信号是斑马鱼胚胎性下丘脑中的神经发生所必需的。我也发现,在斑马鱼中,Wnt信号和下丘脑神经发生持续到它的成年。这项研究的目标就是确定Wnt信号在神经发生中的特异性作用。”
在这项研究中,Dorsky和他的同事们证实在斑马鱼胚胎中,Wnt信号存在神经前体细胞之中,其中这些神经前体细胞正在下丘脑中活跃地增殖。这些前体细胞拥有分裂和分化为多种特殊细胞类型的潜力。他们还发现Wnt信号也是一生当中进行下丘脑神经发生所必需的。
研究人员还发现Wnt信号通路在斑马鱼胚胎和成体之间发挥的作用有所不同。在斑马鱼胚胎中,激活Wnt信号是神经前体细胞增殖必需的,其中这种增殖促进大脑结构生长。然而,在发育较后的阶段(包括成年时)中,Wnt信号必须保持活性,才能让神经前体细胞分化为神经细胞,然后在这些细胞完成分化过程之后,则需要抑制这种信号。值得注意的是,研究人员也发现小鼠也表现出类似于斑马鱼的Wnt活性。(生物谷Bioon.com)
doi: 10.1016/j.devcel.2012.07.012
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Wnt Signaling Regulates Postembryonic Hypothalamic Progenitor Differentiation
Xu Wang, Daniel Kopinke, Junji Lin, Adam D. McPherson, Robert N. Duncan, Hideo Otsuna, Enrico Moro, Kazuyuki Hoshijima, David J. Grunwald, Francesco Argenton, Chi-Bin Chien, L. Charles Murtaugh, Richard I. Dorsky
During angiogenesis, nascent vascular sprouts fuse to form vascular networks, enabling efficient circulation. Mechanisms that stabilize the vascular plexus are not well understood. Sphingosine 1-phosphate (S1P) is a blood-borne lipid mediator implicated in the regulation of vascular and immune systems. Here we describe a mechanism by which the G protein-coupled S1P receptor-1 (S1P1) stabilizes the primary vascular network. A gradient of S1P1 expression from the mature regions of the vascular network to the growing vascular front was observed. In the absence of endothelial S1P1, adherens junctions are destabilized, barrier function is breached, and flow is perturbed, resulting in abnormal vascular hypersprouting. Interestingly, S1P1 responds to S1P as well as laminar shear stress to transduce flow-mediated signaling in endothelial cells both in vitro and in vivo. These data demonstrate that blood flow and circulating S1P activate endothelial S1P1 to stabilize blood vessels in development and homeostasis