Notch-dependent induction of left/right asymmetry in C. elegans interneurons and motoneurons.
Notch-dependent induction of left/right asymmetry in C. elegans interneurons and motoneurons.
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DOI：
10.1016/j.cub.2011.06.016
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发表时间：
2011-07-26
期刊：
影响因子：
9.2
通讯作者：
Hobert, Oliver
中科院分区：
文献类型：
--
作者：
Bertrand, Vincent;Bisso, Paul;Poole, Richard J.;Hobert, Oliver
虽然无脊椎动物和脊椎动物的神经系统在结构水平上基本上是双侧对称的，但它们显示出显著程度的功能性左/右（L/R）不对称。在秀丽隐杆线虫中，两对结构对称的感觉神经元，ASE和AWC显示不同类型的功能性L/R不对称性（定型与随机不对称性），这是由不同的分子机制控制的。除了这两种情况，在C。线虫神经系统以及控制其他潜在不对称性的机制的类型和多样性仍有待确定。在这里，我们报告的β 3/寡聚体型bHLH转录因子hLH-16是L/R不对称表达在几个不同的，否则两侧对称的中间神经元和运动神经元对。这些神经元对是控制C的已知电路的一部分。elegans导航我们发现，hlh-16的不对称性是在原肠胚形成过程中由源自中胚层的不对称LAG-2/Delta信号产生的。该信号通过Notch效应物LAG-1/Su（H）/CBF与hlh-16基因座中的顺式调节元件的直接结合来促进左侧神经元中的hlh-16表达。通过去除hlh-16，我们揭示了AIY中间神经元的轴突延伸到神经环中的能力的意外不对称性，其中左侧AIY轴突需要升高的hlh-16表达以进行正确的延伸。综上所述，我们的研究表明，分子L/R不对称的程度在C。elegans神经系统比以前预期的更广泛，它建立了一种新的信号传导机制，跨越胚层使双侧对称神经元谱系多样化，并揭示了双侧对称神经元轴突生长的L/R不对称控制。
Although invertebrate and vertebrate nervous systems are largely bilateral symmetric on a structural level, they display striking degrees of functional left/right (L/R) asymmetry. In Caenorhabditis elegans two structurally symmetric pairs of sensory neurons, ASE and AWC display distinct types of functional L/R asymmetry (stereotyped vs. stochastic asymmetry), which are controlled by distinct molecular mechanisms. Beyond these two cases, the extent of neuronal asymmetry in the C. elegans nervous system and the types and diversities of mechanisms that control other potential asymmetries remain to be determined. Here, we report that the Beta3/Olig-type bHLH transcription factor hlh-16 is L/R asymmetrically expressed in several distinct, otherwise bilaterally symmetric interneuron and motoneuron pairs. These neuron pairs are part of a known circuit controlling C. elegans navigation. We find that hlh-16 asymmetry is generated during gastrulation by an asymmetric LAG-2/Delta signal originating from the mesoderm. This signal promotes hlh-16 expression in neurons on the left side through direct binding of the Notch effector LAG-1/Su(H)/CBF to a cis-regulatory element in the hlh-16 locus. Through the removal of hlh-16 we reveal an unanticipated asymmetry in the ability of the axons of the AIY interneurons to extend into the nerve ring, with the left AIY axon requiring elevated hlh-16 expression for correct extension. Taken together, our study suggests that the extent of molecular L/R asymmetry in the C. elegans nervous system is broader than previously anticipated, it establishes a novel signaling mechanism that crosses germ layers to diversify bilaterally symmetric neuronal lineages, and reveals L/R asymmetric control of axonal outgrowth of bilaterally symmetric neurons.
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影响因子：
64.8
作者：
Suzuki, Hiroshi;Thiele, Tod R.;Faumont, Serge;Ezcurra, Marina;Lockery, Shawn R.;Schafer, William R.
通讯作者：
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DOI：
10.1016/j.cub.2009.05.043
发表时间：
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期刊：
Current biology : CB
影响因子：
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作者：
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影响因子：
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作者：
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影响因子：
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作者：
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Hobert, Oliver
DOI：
10.1073/pnas.0409009101
发表时间：
2005-03-01
影响因子：
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作者：
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通讯作者：
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