Developmental changes in expression, subcellular distribution, and function of Drosophila N-cadherin, guided by a cell-intrinsic program during neuronal differentiation.

Developmental changes in expression, subcellular distribution, and function of Drosophila N-cadherin, guided by a cell-intrinsic program during neuronal differentiation.
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DOI:
10.1016/j.ydbio.2012.04.006
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发表时间:
2012-06-15
影响因子:
2.7
通讯作者:
Suzuki E
Suzuki E
中科院分区:
生物学3区
文献类型:
--
作者:
Kurusu M;Katsuki T;Zinn K;Suzuki E

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细胞粘附分子(CAM)在神经发育过程中发挥着多种功能。单个CAM在神经元分化的每个阶段都可以发挥不同的作用;然而,人们对这种功能转换是如何完成的知之甚少。在这里,我们表明,果蝇N-钙粘蛋白(CadN)是需要在多个发展阶段在同一个神经元的人口,其亚细胞表达模式的变化之间的不同阶段。在蘑菇体神经元和运动神经元的发育过程中,CadN在生长的轴突上以高水平表达,而在成熟神经元中表达下调并限于突触位点。CadN突变体的表型分析表明,发展中的轴突需要CadN轴突的指导和fasciculation,而成熟的神经元的终端生长和受体聚集。此外,我们证明,CadN下调可以在培养的神经元中实现,而不与其他细胞的突触接触。使用Kir2.1的神经元沉默实验表明,神经元兴奋性也与体内CadN下调有关。有趣的是,在发育中的神经元中,非选择性阳离子通道dTRPA 1的异位表达可以过早地诱导CadN的下调。总之,我们认为在神经元分化过程中CadN表达的转换涉及神经元内调节的阳离子流入。
Cell adhesion molecules (CAMs) perform numerous functions during neural development. An individual CAM can play different roles during each stage of neuronal differentiation; however, little is known about how such functional switching is accomplished. Here we show that Drosophila N-cadherin (CadN) is required at multiple developmental stages within the same neuronal population and that its sub-cellular expression pattern changes between the different stages. During development of mushroom body neurons and motoneurons, CadN is expressed at high levels on growing axons, whereas expression becomes downregulated and restricted to synaptic sites in mature neurons. Phenotypic analysis of CadN mutants reveals that developing axons require CadN for axon guidance and fasciculation, whereas mature neurons for terminal growth and receptor clustering. Furthermore, we demonstrate that CadN downregulation can be achieved in cultured neurons without synaptic contact with other cells. Neuronal silencing experiments using Kir2.1 indicate that neuronal excitability is also dispensable for CadN downregulation in vivo. Interestingly, downregulation of CadN can be prematurely induced by ectopic expression of a nonselective cation channel, dTRPA1, in developing neurons. Together, we suggest that switching of CadN expression during neuronal differentiation involves regulated cation influx within neurons.
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