Brain Institute, Federal University of Rio Grande do Norte Natal, Brazil.
Department of Biosystems Science and Engineering, Cell Systems Dynamics, ETH Zurich Basel, Switzerland.
Front Cell Neurosci. 2014 Mar 11;8:77. doi: 10.3389/fncel.2014.00077. eCollection 2014.
The morphogen Sonic Hedgehog (SHH) plays a critical role in the development of different tissues. In the central nervous system, SHH is well known to contribute to the patterning of the spinal cord and separation of the brain hemispheres. In addition, it has recently been shown that SHH signaling also contributes to the patterning of the telencephalon and establishment of adult neurogenic niches. In this work, we investigated whether SHH signaling influences the behavior of neural progenitors isolated from the dorsal telencephalon, which generate excitatory neurons and macroglial cells in vitro. We observed that SHH increases proliferation of cortical progenitors and generation of astrocytes, whereas blocking SHH signaling with cyclopamine has opposite effects. In both cases, generation of neurons did not seem to be affected. However, cell survival was broadly affected by blockade of SHH signaling. SHH effects were related to three different cell phenomena: mode of cell division, cell cycle length and cell growth. Together, our data in vitro demonstrate that SHH signaling controls cell behaviors that are important for proliferation of cerebral cortex progenitors, as well as differentiation and survival of neurons and astroglial cells.
形态发生素 Sonic Hedgehog（SHH）在不同组织的发育中起着关键作用。在中枢神经系统中，SHH 被广泛认为有助于脊髓的模式形成和大脑半球的分离。此外，最近的研究表明，SHH 信号通路也有助于端脑的模式形成和成年神经发生龛的建立。在这项工作中，我们研究了 SHH 信号通路是否影响从背侧端脑分离出的神经祖细胞的行为，这些祖细胞在体外可产生兴奋性神经元和大胶质细胞。我们观察到 SHH 增加了皮质祖细胞的增殖和星形胶质细胞的生成，而用环巴胺阻断 SHH 信号通路则有相反的效果。在这两种情况下，神经元的生成似乎都没有受到影响。然而，细胞存活受到 SHH 信号通路阻断的广泛影响。SHH 的作用与三种不同的细胞现象有关：细胞分裂方式、细胞周期长度和细胞生长。总之，我们的体外数据表明，SHH 信号通路控制着与大脑皮质祖细胞增殖以及神经元和星形胶质细胞分化和存活有关的细胞行为。
