lin-12 Notch functions in the adult nervous system of C. elegans.
lin-12 Notch functions in the adult nervous system of C. elegans.
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DOI：
10.1186/1471-2202-6-45
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发表时间：
2005-07-12
期刊：
影响因子：
2.4
通讯作者：
Hart AC
中科院分区：
文献类型：
--
作者：
Chao MY;Larkins-Ford J;Tucey TM;Hart AC
Notch信号通路在物种间是保守的，传统上与胚胎发育期间的细胞命运决定有关。Notch信号成分也在成年小鼠和果蝇的大脑中发育后表达。最近的研究表明，Notch信号可能在神经元的生理而非发育调节中发挥作用。在这里，我们调查了一个新的非发育作用秀丽隐杆线虫lin-12 Notch信号在神经元调节自发逆转率在运动过程中。C.在正常的运动过程中是恒定的。与野生型对照相比，lin-12功能获得和丧失突变动物的逆转率均显著增加。这些缺陷是由lin-12活性引起的，因为野生型lin-12转基因可以挽救功能缺陷的丧失。此外，lin-12的过度表达再现了功能获得性缺陷。在发育后的成年动物中增加或减少lin-12的活性足以快速和可逆地增加逆转，从而排除lin-12的发育作用。虽然lin-12在外阴和体细胞性腺谱系中表达，但我们发现这些组织在调节逆转率方面没有作用。相反，改变lin-12在神经系统中的活性就足以增加逆转。这些行为变化需要经典lin-12信号级联的组成部分，包括配体lag-2和转录效应子lag-1。最后，C.秀丽线虫AMPA/红藻氨酸谷氨酸受体同源物glr-1显示与lin-12的强遗传相互作用，表明glr-1和/或其它谷氨酸门控通道可能是lin-12调节的靶。我们的结果表明lin-12 Notch在C. Elegans，并表明LIN-12急性调节神经元生理学以调节动物行为，而不改变神经元细胞命运特化或神经突生长。这与Notch信号传导在具有迟发症状的神经系统疾病中的作用一致。
Notch signaling pathways are conserved across species and traditionally have been implicated in cell fate determination during embryonic development. Notch signaling components are also expressed postdevelopmentally in the brains of adult mice and Drosophila. Recent studies suggest that Notch signaling may play a role in the physiological, rather than developmental, regulation of neurons. Here, we investigate a new non-developmental role for Caenorhabditis elegans lin-12 Notch signaling in neurons regulating the spontaneous reversal rate during locomotion. The spontaneous reversal rate of C. elegans during normal locomotion is constant. Both lin-12 gain and loss of function mutant animals had significantly increased reversal rates compared to wild type controls. These defects were caused by lin-12 activity, because the loss of function defect could be rescued by a wild type lin-12 transgene. Furthermore, overexpression of lin-12 recapitulated the gain-of-function defect. Increasing or decreasing lin-12 activity in the postdevelopmental adult animal was sufficient to rapidly and reversibly increase reversals, thereby excluding a developmental role for lin-12. Although lin-12 is expressed in the vulval and somatic gonad lineages, we find that these tissues play no role in regulating reversal rates. In contrast, altering lin-12 activity specifically in the nervous system was sufficient to increase reversals. These behavioral changes require components of the canonical lin-12 signaling cascade, including the ligand lag-2 and the transcriptional effector lag-1. Finally, the C. elegans AMPA/kainate glutamate receptor homolog glr-1 shows strong genetic interactions with lin-12, suggesting that glr-1 and/or other glutamate gated channels may be targets of lin-12 regulation. Our results demonstrate a neuronal role for lin-12 Notch in C. elegans and suggest that lin-12 acutely regulates neuronal physiology to modulate animal behavior, without altering neuronal cell fate specification or neurite outgrowth. This is consistent with a role for Notch signaling in neurological disease with late onset symptoms.
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影响因子：
10.5
作者：
FLEMING, RJ;SCOTTGALE, TN;ARTAVANISTSAKONAS, S
通讯作者：
ARTAVANISTSAKONAS, S
影响因子：
7.8
作者：
JOHANSEN, KM;FEHON, RG;ARTAVANISTSAKONAS, S
通讯作者：
ARTAVANISTSAKONAS, S
影响因子：
9.2
作者：
Costa, RM;Honjo, T;Silva, AJ
通讯作者：
Silva, AJ
影响因子：
56.9
作者：
Feinberg, EH;Hunter, CP
通讯作者：
Hunter, CP
影响因子：
64.8
作者：
HART, AC;SIMS, S;KAPLAN, JM
通讯作者：
KAPLAN, JM