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首页> 外文期刊>eLife journal >Specific polar subpopulations of astral microtubules control spindle orientation and symmetric neural stem cell division
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Specific polar subpopulations of astral microtubules control spindle orientation and symmetric neural stem cell division

机译：星状微管的特定极性亚群控制纺锤体定向和对称神经干细胞分裂

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A stem cell can divide in two ways. Either it can split symmetrically into two identical daughter stem cells, or it can split asymmetrically into a stem cell and a specialist cell. The structure that forms inside the dividing cell to separate pairs of chromosomes—called the mitotic spindle—also partitions the molecules that determine what kind of cell each daughter cell will become. The mitotic spindle is made up of protein microtubules. Astral microtubules connect the spindle to a structure found at the inner face of the cell membrane called the cell cortex. This helps the spindle to orient itself correctly and control the plane of cell division. This is particularly important in cells that are different at their top and bottom, like polarized neural stem cells. To divide symmetrically, these cells need to split vertically from top to bottom. Then, to divide asymmetrically they tilt the cell division plane off-vertical. Classical studies on neuroblasts from the fruit fly Drosophila have shown that a big, 90° reorientation, from vertical to horizontal underlies this change. However, in the primary stem cells of the mammalian brain, subtle off-vertical tilting suffices for asymmetric divisions to occur. This tilting must be finely regulated if not, neurodevelopmental disorders, such as microcephaly and lissencephaly, may arise. Mora-Bermúdez et al. investigated how mammalian cortical stem cells control such subtle spindle orientation changes by taking images of developing brain tissue from genetically modified mice. These show that not all astral microtubules affect whether the spindle reorients, as was previously thought. Instead, only those connecting the spindle to the cell cortex at the top and bottom of the cell—the apical/basal astrals—are involved. A decrease in the number of apical/basal astrals enables the spindle to undergo small reorientations. Mora-Bermúdez et al. therefore propose a model in which the spindle becomes less strongly anchored when the number of apical/basal astrals is reduced. This makes the spindle easier to tilt, allowing neural stem cells to undergo asymmetric divisions to produce neurons. The decrease in the number of apical/basal astrals appears to be caused by a reduction in the amount of a molecule that is known to help link the microtubules to the cell cortex. This reduction occurs only in the cortex at the top of the cell. Mora-Bermúdez et al. were also able to manipulate this process by adding very low doses of a microtubule inhibitor called nocodazole, which reduced the number of only the apical/basal astrals, increasing the ability of the spindle to reorient.
机译：干细胞可以两种方式分裂。它可以对称地分裂成两个相同的子干细胞，也可以不对称地分裂成一个干细胞和一个特殊细胞。在分裂细胞内部形成分离成对染色体的结构（称为有丝分裂纺锤体），还对决定每个子细胞将变成哪种细胞的分子进行分区。有丝分裂纺锤体由蛋白质微管组成。星状微管将纺锤体连接到位于细胞膜内表面的结构，称为细胞皮层。这有助于主轴正确定向并控制细胞分裂的平面。这在极化的神经干细胞等顶部和底部不同的细胞中尤其重要。为了对称划分，这些单元需要从顶部到底部垂直拆分。然后，为了不对称地划分，他们将单元划分平面倾斜为不垂直。对果蝇果蝇的神经母细胞进行的经典研究表明，从垂直到水平的90°大重新定向是这种变化的基础。然而，在哺乳动物大脑的主要干细胞中，微妙的垂直外倾斜足以发生不对称分裂。如果没有，则必须对这种倾斜进行精细调节，否则可能会引起神经发育障碍，例如小头畸形和小头畸形。 Mora-Bermúdez等。通过拍摄转基因小鼠的大脑组织发育图像，研究了哺乳动物皮质干细胞如何控制这种微妙的纺锤体方向变化。这些表明，并非所有的星形微管都会影响纺锤体是否重新定向，如先前所认为的那样。相反，仅涉及将纺锤体连接到细胞顶部和底部的细胞皮质的那些（顶/基星体）。顶部/底部星体数量的减少使心轴能够进行较小的重新定向。 Mora-Bermúdez等。因此，提出了一种模型，其中当减少顶/基星基的数量时，主轴的锚定强度降低。这使主轴更容易倾斜，从而使神经干细胞进行不对称分裂以产生神经元。顶/基底星体数量的减少似乎是由于已知有助于将微管连接到细胞皮层的分子数量减少所致。这种减少仅发生在细胞顶部的皮质中。 Mora-Bermúdez等。它们还可以通过添加极低剂量的微管抑制剂Nocodazole来操纵这一过程，该抑制剂可减少仅顶端/基底星体的数量，从而增加纺锤体重新定向的能力。

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