Pyramidal neuron polarity axis is defined at the bipolar stage

Pyramidal neuron polarity axis is defined at the bipolar stage
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DOI:
10.1242/jcs.023143
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发表时间:
2008-01-15
影响因子:
4
通讯作者:
Dotti, Carlos G.
Dotti, Carlos G.
中科院分区:
生物学2区
文献类型:
--
作者:
de Anda, Froylan Calderon;Gaertner, Annette;Dotti, Carlos G.

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海马和皮质神经元的发育的原位观察表明,最终的轴突树突身份是在前两个相反位置的神经突产生时定义的。完全不同的是,体外研究表明,轴突的命运是由随机选择的多个小神经突之一的快速生长。通过分析所有神经突的命运,从细胞体出现的时间开始,我们证明了极性是在双极阶段定义的,两个第一次出现的神经突之一获得轴突的命运,不管有多少其他神经突后来形成。在体内,前两个神经突具有最高的生长潜力,因为切割轴突导致在相反极的神经突生长新的轴突,并且切割该轴突诱导从第一个再生。极化生长的这种时空层次定义,连同微管动力学的双极组织和在其之前的膜运输,与由内在程序启动的极性一致。在这种情况下,轴突特化所需的分子将作用于前两个神经突之一,而最终的极性承诺将需要外部线索。
In situ observations of the development of hippocampal and cortical neurons indicate that final axon-dendrite identity is defined at the time of generation of the first two, oppositely positioned, neurites. Quite differently, in vitro studies demonstrated that axonal fate is defined by the stochastic selection of one of the multiple minor neurites for fast outgrowth. By analyzing the fate of all neurites, starting at the time of emergence from the cell body, we demonstrate that polarity is defined at the bipolar stage, with one of the two first-appearing neurites acquiring axonal fate, irrespective of how many other neurites later form. The first two neurites have, as in vivo, the highest growth potential, as cutting the axon results in the growth of a new axon from the neurite at the opposite pole, and cutting this induces regrowth from the first. This temporal and spatial hierarchical definition of polarized growth, together with the bipolar organization of microtubule dynamics and membrane transport preceding it, is consistent with polarity being initiated by an intrinsic program. In this scenario, molecules required for axon specification would act at one of the first two neurites and extrinsic cues will be required for final commitment of polarity.