推荐:转引自生物谷:神经系统细胞不对称发育分化的机理被揭示

神经系统细胞不对称发育分化的机理被揭示
［ 作者：佚名 转贴自：本站原创 点击数：118 更新时间：2004-3-3 编辑：admin ］


生物谷报道：机体的不对称发育情况十分常见，在神经系统中表现十分广泛，左右大脑皮层功能是不同的等，那么其中的机理是什么呢？在发育过程中，哪个基因或哪一群基因是控制开关？这几篇文章揭示这个秘密。

Numb, an important regulator of asymmetric cell division and cell-fate determination, has been implicated in different aspects of neural development in mammals. But the traditional approach of eliminating the expression of a gene to investigate its functional role has not been particularly informative in the case of Numb, as knockout mice die early in embryogenesis. Two research groups have now circumvented this problem by generating conditional Numb-knockout mice in which expression is selectively abolished in restricted areas of the neural tube.




Klein et al. ablated the Numb gene in neuroepithelial cells of the midbrain–hindbrain boundary using the Cre–lox system. Specifically, they crossed mice in which Numb was flanked by loxP sequences with mice in which Cre recombinase — an enzyme necessary for recombination at loxP sites — was under the transcriptional control of the engrailed-2 promoter, which is characteristic of the midbrain–hindbrain boundary. After recombination, Numb was absent only cells in which engrailed-2 was active.

The authors focused their attention on the development of the cerebellum, which originates from the midbrain–hindbrain boundary. They found that the absence of Numb in the mutant mice led to a delay in the maturation of mitotic precursors into granule cells and in the subsequent migration of this cell type into the granule cell layer, but had no effect on the proliferation of precursors. In addition, the elimination of Numb resulted in a delay in the maturation and layered organization of Purkinje cells, which might be a consequence of both the abnormal development of granule cells and the absence of Numb itself. Ultimately, these defects led to macroscopic cerebellar defects such as abnormal foliation and reduced size.

In the second study, Li et al. used a similar system for the generation of conditional knockouts, but focused on the dorsal forebrain by using the Emx1 promoter. These authors were also interested in the possibility of redundant functions of Numb and its homologue Numblike. They therefore generated the conditional knockout mice in a Numblike-null background. In addition, the use of the Emx1 promoter, which is active from embryonic day (E) 9.5, enabled them to study the role of Numb in the second wave of cortical neurogenesis, which occurs from E12.5, while sparing the first wave, which starts from E8.5. Li et al. found increased proliferation and apoptosis of neural precursors in the double-mutant animals — phenotypes that were accompanied by a reduction in the differentiation of these progenitors into neurons and by abnormalities in the morphogenesis of the cortex.

Despite the clear differences in genetic background between the animals that were used in both studies, the data disclose a critical role for Numb in the differentiation of mitotic precursors into mature neurons in two brain regions. However, the underlying mechanisms might be markedly different, as indicated by the differential effect of the mutation on precursor proliferation in the cortex and the cerebellum. Considering the large number of potential binding partners that have been described for Numb, there is scope for multiple downstream signalling mechanisms that might mediate its action, but unravelling them will constitute a considerable experimental challenge.

好东东[em72]

只能是部分被揭示吧，怎能一叶障目不见泰山呢？

[em5]
生物体的发育更复杂了。
能不能认为不对称发育将会成为进化的一个新的方向呢？