LIN-44/Wnt directs dendrite outgrowth through LIN-17/Frizzled in C. elegans Neurons.
LIN-44/Wnt directs dendrite outgrowth through LIN-17/Frizzled in C. elegans Neurons.
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DOI：
10.1371/journal.pbio.1001157
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发表时间：
2011-09
期刊：
影响因子：
9.8
通讯作者：
Hilliard MA
中科院分区：
文献类型：
--
作者：
Kirszenblat L;Pattabiraman D;Hilliard MA
神经系统功能需要神经元、轴突和树突的两个功能和形态领域的适当发育。虽然这两个领域对信号传输同样重要，但我们对树突发育的理解仍然相对较差。在这里，我们在C中展示了这一点。在线虫中，Wnt配体LIN-44及其卷曲受体LIN-17调节PQR氧感觉神经元的树突发育。在lin-44和lin-17突变体中，PQR树枝状突起无法形成、生长发育不良或路线错误。LIN-44的时间和空间表达的操作，结合细胞消融实验，表明该分子在胚胎发生过程中形成图案，并作为一个有吸引力的线索来定义树突出现的位点。lin-44和lin-17之间的遗传相互作用表明，LIN-44信号通过LIN-17受体传递，该受体在PQR中自主作用于细胞。此外，我们提供的证据表明，LIN-17与另一种Wnt分子EGL-20相互作用，并在此过程中与Wnt-1/Frizzled平行发挥作用。总之，我们的研究结果揭示了Wnt和Frizzled分子在体内调节树突发育中的关键作用。神经元具有不同的隔室，其包括轴突和树突。这两个区室对于神经元之间的通信是必不可少的，因为信号由树突接收并由轴突传输。虽然树突对于神经连接至关重要，但人们对它们是如何形成的知之甚少。在这里，我们研究了树突如何在体内发展，通过检查一个氧感觉神经元（PQR）在线虫C。优雅使用遗传学方法，我们已经发现，Wnt蛋白，一组高度保守的分泌型形态发生素，与它们的典型卷曲受体相互作用，以控制PQR树突的发育。我们发现，Wnt分子作为有吸引力的信号，以确定树枝晶生长的起始和方向。有趣的是，Wnt蛋白特异性作用于树突而不影响轴突，这表明树突的生长可以通过独立于轴突形成的不同过程来调节。我们预测，类似的机制可能是在其他物种由于Wnt和卷曲分子在发展中的保守作用。
Nervous system function requires proper development of two functional and morphological domains of neurons, axons and dendrites. Although both these domains are equally important for signal transmission, our understanding of dendrite development remains relatively poor. Here, we show that in C. elegans the Wnt ligand, LIN-44, and its Frizzled receptor, LIN-17, regulate dendrite development of the PQR oxygen sensory neuron. In lin-44 and lin-17 mutants, PQR dendrites fail to form, display stunted growth, or are misrouted. Manipulation of temporal and spatial expression of LIN-44, combined with cell-ablation experiments, indicates that this molecule is patterned during embryogenesis and acts as an attractive cue to define the site from which the dendrite emerges. Genetic interaction between lin-44 and lin-17 suggests that the LIN-44 signal is transmitted through the LIN-17 receptor, which acts cell autonomously in PQR. Furthermore, we provide evidence that LIN-17 interacts with another Wnt molecule, EGL-20, and functions in parallel to MIG-1/Frizzled in this process. Taken together, our results reveal a crucial role for Wnt and Frizzled molecules in regulating dendrite development in vivo. Neurons have distinct compartments, which include axons and dendrites. Both of these compartments are essential for communication between neurons, as signals are received by dendrites and transmitted by axons. Although dendrites are vital for neural connectivity, very little is known about how they are formed. Here, we have investigated how dendrites develop in vivo by examining an oxygen sensory neuron (PQR) in the nematode C. elegans. Using a genetic approach, we have discovered that Wnt proteins, a group of highly conserved secreted morphogens, interact with their canonical Frizzled receptors to control the development of the PQR dendrite. We show that Wnt molecules act as attractive signals to determine the initiation and direction of dendrite outgrowth. Interestingly, Wnt proteins act specifically on the dendrite without affecting the axon, suggesting that outgrowth of the dendrite can be regulated by distinct processes that are independent of axon formation. We predict that similar mechanisms may be in place in other species owing to the conserved roles of Wnt and Frizzled molecules in development.
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影响因子：
64.5
作者：
Inoue, T;Oz, HS;Sternberg, PW
通讯作者：
Sternberg, PW
影响因子：
25
作者：
Liu, YB;Shi, J;Zou, YM
通讯作者：
Zou, YM
影响因子：
2.7
作者：
HEDGECOCK, EM;CULOTTI, JG;PERKINS, LA
通讯作者：
PERKINS, LA
DOI：
10.1126/science.1189095
发表时间：
2010-06-04
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Oren-Suissa M;Hall DH;Treinin M;Shemer G;Podbilewicz B
通讯作者：
Podbilewicz B
影响因子：
64.5
作者：
HERMAN, MA;VASSILIEVA, LL;HERMAN, RK
通讯作者：
HERMAN, RK