2012年9月12日 訊 /生物谷BIOON/ --來自美國猶他大學(xué)的研究人員對調(diào)節(jié)下丘腦中成體神經(jīng)細胞再生方面獲得新的深入認(rèn)識。根據(jù)9月12日刊登在Developmental Cell期刊上的一篇論文,,他們報道,一種被稱作Wnt信號通路的細胞間通信網(wǎng)絡(luò)在下丘腦中神經(jīng)前體細胞產(chǎn)生和特化中發(fā)揮著重要作用,。
論文通信作者Richard Dorsky博士說,“在我們早期的研究中,我們發(fā)現(xiàn)Wnt信號是斑馬魚胚胎性下丘腦中的神經(jīng)發(fā)生所必需的,。我也發(fā)現(xiàn),在斑馬魚中,,Wnt信號和下丘腦神經(jīng)發(fā)生持續(xù)到它的成年。這項研究的目標(biāo)就是確定Wnt信號在神經(jīng)發(fā)生中的特異性作用,。”
在這項研究中,Dorsky和他的同事們證實在斑馬魚胚胎中,,Wnt信號存在神經(jīng)前體細胞之中,,其中這些神經(jīng)前體細胞正在下丘腦中活躍地增殖,。這些前體細胞擁有分裂和分化為多種特殊細胞類型的潛力,。他們還發(fā)現(xiàn)Wnt信號也是一生當(dāng)中進行下丘腦神經(jīng)發(fā)生所必需的。
研究人員還發(fā)現(xiàn)Wnt信號通路在斑馬魚胚胎和成體之間發(fā)揮的作用有所不同,。在斑馬魚胚胎中,激活Wnt信號是神經(jīng)前體細胞增殖必需的,,其中這種增殖促進大腦結(jié)構(gòu)生長。然而,,在發(fā)育較后的階段(包括成年時)中,,Wnt信號必須保持活性,才能讓神經(jīng)前體細胞分化為神經(jīng)細胞,,然后在這些細胞完成分化過程之后,則需要抑制這種信號,。值得注意的是,研究人員也發(fā)現(xiàn)小鼠也表現(xiàn)出類似于斑馬魚的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