Small-molecule-mediated axonal branching in Caenorhabditis elegans.
Small-molecule-mediated axonal branching in Caenorhabditis elegans.
复制标题
秀丽隐杆线虫中小分子介导的轴突分支。
DOI:
10.1002/cbic.201200712
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发表时间:
2013
期刊:
影响因子:
--
通讯作者:
Siegel,Dionicio
中科院分区:
文献类型:
--
作者:
Zlotkowski,Katherine;Pierce-Shimomura,Jon;Siegel,Dionicio
The complex synaptic connectivity of neuronal circuits enables our abilities to apprehend our environment, to act, and to remember. The formation of these neuronal networks both during development and in adulthood is coordinated through axonal branching, which permits a single neuron to relay information through its axon to multiple coupled neurons. This process is highly regulated and leads to the targeting and plasticity of neuronal circuits. The formation of branches from the axonal shaft is initiated by the protrusion of filopodia or lamellipodia that require subsequent stabilization,[1–3] as the dynamic nature of the newly formed branch allows either continued growth or retraction back into the axon.[4–6] The initiation and stabilization of branches can lead to the formation of new, functional neuronal circuits. Agents that can promote post-developmental axonal branching hold promise in the discovery of treatments for disorders caused by defects in connectivity that occur during development. Additionally, the induction of branching can promote the regeneration of axonal connections that have been damaged due to disease or injury.[7]The majority of screens to identify small molecules that are capable of promoting the survival and growth of neurons employ in vitro systems that utilize cell lines or primary neuronal cultures. These assays, although straightforward, fail to reflect the conditions of networked neurons and do not account for metabolism, drug access to specific tissues, or toxicity. To develop a straightforward, easily implemented assay that reflects the outgrowth of networked neurons in vivo, we have established a new protocol utilizing the nematode Caenorhabditis elegans. The complete mapping of the roundworm's 302 neurons makes the organism ideal for these studies.[8] A number of important conserved biological functions, such as apoptosis, have been elucidated through studies using C. elegans.[9] Additionally,