Haubst Nicole, Georges-Labouesse Elisabeth, De Arcangelis Adele, Mayer Ulrike, Götz Magdalena
Institute for Stem Cell Research, GSF, National Research Center for Environment and Health, Ingolstädter Landstr.1, D-85764 Neuherberg/Munich, Germany.
Development. 2006 Aug;133(16):3245-54. doi: 10.1242/dev.02486.
Radial glial cells have been shown to act as neuronal precursors in the developing cortex and to maintain their radial processes attached to the basement membrane (BM) during cell division. Here, we examined a potential role of direct signalling from the BM to radial glial cells in three mouse mutants where radial glia attachment to the BM is disrupted. This is the case if the nidogen-binding site of the laminin gamma1 chain is mutated, in the absence of alpha6 integrin or of perlecan, an essential BM component. Surprisingly, cortical radial glial cells lacking contact to the BM were not affected in their proliferation, interkinetic nuclear migration, orientation of cell division and neurogenesis. Only a small subset of precursors was located ectopically within the cortical parenchyma. Notably, however, neuronal subtype composition was severely disturbed at late developmental stages (E18) in the cortex of the laminin gamma1III4-/- mice. Thus, although BM attachment seems dispensable for precursor cells, an intact BM is required for adequate neuronal composition of the cerebral cortex.
放射状胶质细胞已被证明在发育中的皮质中充当神经元前体,并在细胞分裂期间保持其放射状突起附着于基底膜(BM)。在此,我们在三种小鼠突变体中研究了从基底膜到放射状胶质细胞的直接信号传导的潜在作用,在这些突变体中,放射状胶质细胞与基底膜的附着被破坏。如果层粘连蛋白γ1链的巢蛋白结合位点发生突变、在缺乏α6整合素或缺乏核心蛋白聚糖(一种重要的基底膜成分)的情况下,就会出现这种情况。令人惊讶的是,与基底膜失去接触的皮质放射状胶质细胞在增殖、核内有丝分裂迁移、细胞分裂方向和神经发生方面并未受到影响。只有一小部分前体异位位于皮质实质内。然而,值得注意的是,在层粘连蛋白γ1III4-/-小鼠皮质的发育后期(E18),神经元亚型组成受到严重干扰。因此,尽管基底膜附着对于前体细胞似乎是可有可无的,但完整的基底膜对于大脑皮质的适当神经元组成是必需的。