Cooper M T, Bray S J
Department of Anatomy, University of Cambridge, Downing Street, CB2 3DY,., Cambridge, UK.
Curr Biol. 2000 Nov 30;10(23):1507-10. doi: 10.1016/s0960-9822(00)00826-5.
The eight photoreceptors in each ommatidium of the Drosophila eye are assembled by a process of recruitment [1,2]. First, the R8 cell is singled out, and then subsequent photoreceptors are added in pairs (R2 and R5, R3 and R4, R1 and R6) until the final R7 cell acquires a neuronal fate. R7 development requires the Sevenless receptor tyrosine kinase which is activated by a ligand from R8 [3]. Here, we report that the specification of R7 requires a second signal that activates Notch. We found that a Notch target gene is expressed in R7 shortly after recruitment. When Notch activity was reduced, the cell was misrouted to an R1/R6 fate. Conversely, when activated Notch was present in the R1/R6 cells, it caused them to adopt R7 fates or, occasionally, cone cell fates. In this context, Notch activity appears to act co-operatively, rather than antagonistically, with the receptor tyrosine kinase/Ras pathway in R7 photoreceptor specification. We propose two models: a ratchet model in which Notch would allow cells to remain competent to respond to sequential rounds of Ras signalling, and a combinatorial model in which Notch and Ras signalling would act together to regulate genes that determine cell fate.
果蝇眼中每个小眼的八个光感受器是通过招募过程组装而成的[1,2]。首先，R8细胞被挑选出来，随后成对添加后续的光感受器（R2和R5、R3和R4、R1和R6），直到最终的R7细胞获得神经元命运。R7的发育需要Sevenless受体酪氨酸激酶，它由来自R8的配体激活[3]。在此，我们报告R7的特化需要第二个激活Notch的信号。我们发现一个Notch靶基因在招募后不久就在R7中表达。当Notch活性降低时，该细胞被错误引导至R1/R6命运。相反，当R1/R6细胞中存在激活的Notch时，它会使它们采用R7命运，或者偶尔采用锥体细胞命运。在这种情况下，Notch活性在R7光感受器特化过程中似乎与受体酪氨酸激酶/Ras途径协同作用，而非拮抗作用。我们提出两种模型：一种棘轮模型，其中Notch将使细胞保持对连续几轮Ras信号作出反应的能力；另一种组合模型，其中Notch和Ras信号将共同作用以调节决定细胞命运的基因。
