Department of Genetics and Development, College of Physicians and Surgeons, Columbia University, New York, New York, United States of America.
PLoS Biol. 2011 Aug;9(8):e1001132. doi: 10.1371/journal.pbio.1001132. Epub 2011 Aug 23.
Receptor tyrosine kinases (RTKs) and Notch (N) proteins are different types of transmembrane receptors that transduce extracellular signals and control cell fate. Here we examine cell fate specification in the Drosophila retina and ask how N acts together with the RTKs Sevenless (Sev) and the EGF receptor (DER) to specify the R7 photoreceptor. The retina is composed of many hundred ommatidia, each of which grows by recruiting surrounding, undifferentiated cells and directing them to particular fates. The R7 photoreceptor derives from a cohort of three cells that are incorporated together following specification of the R2-R5 and R8 photoreceptors. Two cells of the cohort are specified as the R1/6 photoreceptor type by DER activation. These cells then activate N in the third cell (the R7 precursor). By manipulation of N and RTK signaling in diverse combinations we establish three roles for N in specifying the R7 fate. The first role is to impose a block to photoreceptor differentiation; a block that DER activation cannot overcome. The second role, paradoxically, is to negate the first; Notch activation up-regulates Sev expression, enabling the presumptive R7 cell to receive an RTK signal from R8 that can override the block. The third role is to specify the cell as an R7 rather than an R1/6 once RTK signaling has specified the cells as a photoreceptor. We speculate why N acts both to block and to facilitate photoreceptor differentiation, and provide a model for how N and RTK signaling act combinatorially to specify the R1/6 and R7 photoreceptors as well as the surrounding non-neuronal cone cells.
受体酪氨酸激酶（RTKs）和 Notch（N）蛋白是两种不同类型的跨膜受体，它们可以传递细胞外信号并控制细胞命运。在这里，我们研究了果蝇视网膜中的细胞命运决定，并探讨了 N 如何与 RTKs Sev（Sev）和 EGF 受体（DER）一起作用以指定 R7 光感受器。视网膜由数百个小眼组成，每个小眼通过招募周围未分化的细胞并将其定向到特定命运来生长。R7 光感受器来源于三个细胞的队列，这些细胞在指定 R2-R5 和 R8 光感受器后一起被招募。该队列中的两个细胞通过 DER 激活被指定为 R1/6 光感受器类型。然后，这些细胞在第三个细胞（R7 前体）中激活 N。通过对 N 和 RTK 信号的各种组合进行操作，我们确定了 N 在指定 R7 命运中的三个作用。第一个作用是施加阻止光感受器分化的作用；这是 DER 激活无法克服的作用。第二个作用是矛盾的； Notch 激活上调 Sev 表达，使假定的 R7 细胞能够从 R8 接收 RTK 信号，从而可以覆盖该阻断。第三个作用是一旦 RTK 信号指定了细胞作为光感受器，就将其指定为 R7 而不是 R1/6。我们推测了 N 为什么既能阻止又能促进光感受器分化，并提供了一个模型，说明了 N 和 RTK 信号如何组合作用以指定 R1/6 和 R7 光感受器以及周围的非神经元圆锥细胞。
