Edenfeld Gundula, Altenhein Benjamin, Zierau Ariane, Cleppien Diana, Krukkert Karin, Technau Gerhard, Klämbt Christian
Institut für Neurobiologie, Universität Münster, Badestr. 9, D-48149 Münster, Germany.
Dev Biol. 2007 Jan 1;301(1):27-37. doi: 10.1016/j.ydbio.2006.11.013. Epub 2006 Nov 10.
A prominent feature of glial cells is their ability to migrate along axons to finally wrap and insulate them. In the embryonic Drosophila PNS, most glial cells are born in the CNS and have to migrate to reach their final destinations. To understand how migration of the peripheral glia is regulated, we have conducted a genetic screen looking for mutants that disrupt the normal glial pattern. Here we present an analysis of two of these mutants: Notch and numb. Complete loss of Notch function leads to an increase in the number of glial cells. Embryos hemizygous for the weak Notch(B-8X) allele display an irregular migration phenotype and mutant glial cells show an increased formation of filopodia-like structures. A similar phenotype occurs in embryos carrying the Notch(ts1) allele when shifted to the restrictive temperature during the glial cell migration phase, suggesting that Notch must be activated during glial migration. This is corroborated by the fact that cell-specific reduction of Notch activity in glial cells by directed numb expression also results in similar migration phenotypes. Since the glial migration phenotypes of Notch and numb mutants resemble each other, our data support a model where the precise temporal and quantitative regulation of Numb and Notch activity is not only required during fate decisions but also later during glial differentiation and migration.
神经胶质细胞的一个显著特征是它们能够沿着轴突迁移,最终包裹并隔离轴突。在胚胎期果蝇的外周神经系统中,大多数神经胶质细胞产生于中枢神经系统,必须迁移才能到达其最终目的地。为了了解外周神经胶质细胞的迁移是如何被调控的,我们进行了一项遗传筛选,寻找破坏正常神经胶质模式的突变体。在这里,我们展示了对其中两个突变体的分析:Notch和numb。Notch功能的完全丧失会导致神经胶质细胞数量增加。携带弱Notch(B-8X)等位基因的半合子胚胎表现出不规则的迁移表型,突变的神经胶质细胞显示丝状伪足样结构的形成增加。当在神经胶质细胞迁移阶段转移到限制温度时,携带Notch(ts1)等位基因的胚胎也会出现类似的表型,这表明在神经胶质细胞迁移过程中Notch必须被激活。通过定向表达numb在神经胶质细胞中特异性降低Notch活性也会导致类似的迁移表型,这一事实证实了这一点。由于Notch和numb突变体的神经胶质细胞迁移表型彼此相似,我们的数据支持这样一个模型,即Numb和Notch活性的精确时间和定量调控不仅在命运决定过程中是必需的,而且在神经胶质细胞分化和迁移后期也是必需的。