Flipping the transcriptional switch from myelin inhibition to axon growth in the CNS.
Flipping the transcriptional switch from myelin inhibition to axon growth in the CNS.
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DOI：
10.3389/fnmol.2015.00034
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发表时间：
2015
影响因子：
4.8
通讯作者：
Hart RP
中科院分区：
文献类型：
--
作者：
Carmel JB;Young W;Hart RP
中枢神经系统（CNS）中切断的轴突再生不良限制了功能恢复。再生失败涉及抑制性环境因素和神经元生长状态的相互作用。为了找到可能克服抑制性环境线索的基因表达的内部变化，我们比较了几种允许在抑制性环境中生长的范例。允许轴突在CNS髓鞘上通过轴突切断和培养的背根神经节（DRG）神经元生长的条件包括不成熟（出生后的最初几天）、高水平的环磷酸腺苷（cAMP）和在外植体前用外周神经损伤进行调节。这种从抑制到生长的转变取决于转录。为了了解允许轴突在CNS中生长的转录组变化，我们与玛丽菲尔宾实验室合作，通过功能获得和功能丧失研究确定了几种功能相关的mRNA。在这个角度来看，我们回顾这些实验的证据，并讨论比较多种再生范式的优点，以确定中枢神经系统轴突再生的核心转录程序。
Poor regeneration of severed axons in the central nervous system (CNS) limits functional recovery. Regeneration failure involves interplay of inhibitory environmental elements and the growth state of the neuron. To find internal changes in gene expression that might overcome inhibitory environmental cues, we compared several paradigms that allow growth in the inhibitory environment. Conditions that allow axon growth by axotomized and cultured dorsal root ganglion (DRG) neurons on CNS myelin include immaturity (the first few postnatal days), high levels of cyclic adenosine mono phosphate (cAMP), and conditioning with a peripheral nerve lesion before explant. This shift from inhibition to growth depends on transcription. Seeking to understand the transcriptome changes that allow axon growth in the CNS, we collaborated with the Marie Filbin laboratory to identify several mRNAs that are functionally relevant, as determined by gain- and loss-of-function studies. In this Perspective, we review evidence from these experiments and discuss the merits of comparing multiple regenerative paradigms to identify a core transcriptional program for CNS axon regeneration.