Polarization of Drosophila Neuroblasts During Asymmetric Division
Polarization of Drosophila Neuroblasts During Asymmetric Division
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DOI：
10.1101/cshperspect.a001388
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发表时间：
2009-08-01
影响因子：
7.2
通讯作者：
Prehoda, Kenneth E.
中科院分区：
文献类型：
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作者：
Prehoda, Kenneth E.
在果蝇发育过程中，神经母细胞分裂产生两种不同命运的后代。一个子细胞自我更新以维持神经母细胞库，而另一个分化以填充中枢神经系统。命运的差异来自于指定自我更新或分化的蛋白质的不对称分布，这是由它们在有丝分裂期间极化成单独的顶端和基底皮质结构域而引起的。神经母细胞的对称性破坏受许多蛋白质的调控，其中许多蛋白质是最近才发现的。非典型蛋白激酶C（aPKC）是一种广泛的极性调节剂，定位于成神经细胞顶端皮质区，并指导基底域的极化。最近的工作表明，极性可以解释在很大程度上由限制aPKC活性的顶端域和那些耦合不对称的aPKC活性的下游因子的极化的机制。极化的aPKC活性由调控分子网络产生，包括Bazooka/Par-3、Cdc 42和抑制基础募集的肿瘤抑制因子Lgl。通过aPKC的直接磷酸化导致皮质释放基底结构域因子，阻止它们占据顶端结构域。在这个框架中，成神经细胞极性产生于一个复杂的系统，该系统协调了强大的aPKC极性，这反过来又通过将磷酸化偶联到皮质释放来极化底物。
During Drosophila development, neuroblasts divide to generate progeny with two different fates. One daughter cell self-renews to maintain the neuroblast pool, whereas the other differentiates to populate the central nervous system. The difference in fate arises from the asymmetric distribution of proteins that specify either self-renewal or differentiation, which is brought about by their polarization into separate apical and basal cortical domains during mitosis. Neuroblast symmetry breaking is regulated by numerous proteins, many of which have only recently been discovered. The atypical protein kinase C (aPKC) is a broad regulator of polarity that localizes to the neuroblast apical cortical region and directs the polarization of the basal domain. Recent work suggests that polarity can be explained in large part by the mechanisms that restrict aPKC activity to the apical domain and those that couple asymmetric aPKC activity to the polarization of downstream factors. Polarized aPKC activity is created by a network of regulatory molecules, including Bazooka/Par-3, Cdc42, and the tumor suppressor Lgl, which represses basal recruitment. Direct phosphorylation by aPKC leads to cortical release of basal domain factors, preventing them from occupying the apical domain. In this framework, neuroblast polarity arises from a complex system that orchestrates robust aPKC polarity, which in turn polarizes substrates by coupling phosphorylation to cortical release.