Wang S, Younger-Shepherd S, Jan L Y, Jan Y N
Howard Hughes Medical Institute, and Department of Physiology, University of California, San Francisco 94143-0724, USA.
Development. 1997 Nov;124(22):4435-46. doi: 10.1242/dev.124.22.4435.
In Drosophila, an adult external sensory organ (bristle) consists of four distinct cells which arise from a sensory organ precursor cell via two rounds of asymmetric divisions. The sensory organ precursor cell first divides to generate two secondary precursor cells, IIa and IIb. The IIa cell then divides to produce the hair cell and the socket cell. Shortly after, the IIb cell divides to generate the neuron and the sheath cell. The membrane-associated protein Numb has been shown to be required for the first two asymmetric divisions. We now report that a new hypomorphic numb mutant not only displays a double-socket phenotype, due to a hair cell to socket cell transformation, but also a double-sheath phenotype, due to a neuron to sheath cell transformation. This provides direct evidence that numb functions in the neuron/sheath cell lineage as well. Those results, together with our observation from immunofluorescence analysis that Numb forms a crescent in the dividing IIa and IIb cells suggest that asymmetric localization of Numb is important for the cell fate determination in all three asymmetric cell divisions in the sensory organ lineage. Interestingly, we found that in the hair/socket cell lineage but not the neuron/sheath cell lineage, a Suppressor of Hairless mutation acts as a dominant suppressor of numb mutations whereas Hairless mutations act as enhancers of numb. Moreover, epistasis analysis indicates that Suppressor of Hairless acts downstream of numb, and results from in vitro binding analysis suggest that the genetic interaction between numb and Hairless may occur through direct protein-protein interaction. These studies reveal that Suppressor of Hairless is required for only a subset of the asymmetric divisions that depend on the function of numb and Notch.
在果蝇中，一个成年外部感觉器官（刚毛）由四个不同的细胞组成，这些细胞通过两轮不对称分裂从一个感觉器官前体细胞产生。感觉器官前体细胞首先分裂产生两个次级前体细胞，即IIa和IIb。然后IIa细胞分裂产生毛细胞和套接细胞。不久之后，IIb细胞分裂产生神经元和鞘细胞。膜相关蛋白Numb已被证明是前两轮不对称分裂所必需的。我们现在报告，一个新的低表达numb突变体不仅由于毛细胞向套接细胞的转变而表现出双套接表型，而且由于神经元向鞘细胞的转变而表现出双鞘表型。这提供了直接证据，表明numb在神经元/鞘细胞谱系中也发挥作用。这些结果，连同我们从免疫荧光分析中观察到的Numb在分裂的IIa和IIb细胞中形成新月形，表明Numb的不对称定位对于感觉器官谱系中所有三个不对称细胞分裂中的细胞命运决定很重要。有趣的是，我们发现，在毛细胞/套接细胞谱系中而不是在神经元/鞘细胞谱系中，无毛抑制因子突变作为numb突变的显性抑制因子，而无毛突变作为numb的增强子。此外，上位性分析表明，无毛抑制因子在numb的下游起作用，体外结合分析的结果表明，numb和无毛之间的遗传相互作用可能通过直接的蛋白质-蛋白质相互作用发生。这些研究表明，无毛抑制因子仅对于依赖numb和Notch功能的一部分不对称分裂是必需的。
