Matakatsu Hitoshi, Blair Seth S
Department of Zoology, University of Wisconsin, 250 North Mills Street, Madison, WI 53706, USA.
Development. 2006 Jun;133(12):2315-24. doi: 10.1242/dev.02401. Epub 2006 May 10.
The protocadherins Fat (Ft) and Dachsous (Ds) are required for several processes in the development of Drosophila, including controlling growth of imaginal discs, planar cell polarity (PCP) and the proximodistal patterning of appendages. Ft and Ds bind in a preferentially heterophilic fashion, and Ds is expressed in distinct patterns along the axes of polarity. It has thus been suggested that Ft and Ds serve not as adhesion molecules, but as receptor and ligand in a poorly understood signaling pathway. To test this hypothesis, we performed a structure-function analysis of Ft and Ds, separating their adhesive and signaling functions. We found that the extracellular domain of Ft is not required for its activity in growth, PCP and proximodistal patterning. Thus, ligand binding is not necessary for Ft activity. By contrast, the extracellular domain of Ds is necessary and sufficient to mediate its effects on PCP, consistent with the model that Ds acts as a ligand during PCP. However, we also provide evidence that Ds can regulate growth independently of Ft, and that the intracellular domain of Ds can affect proximodistal patterning, both suggestive of functions independent of binding Ft. Finally, we show that ft mutants or a dominant-negative Ft construct can affect disc growth without changes in the expression of wingless and Wingless target genes.
原钙黏蛋白Fat（Ft）和Dachsous（Ds）在果蝇发育的多个过程中发挥作用，包括控制成虫盘生长、平面细胞极性（PCP）以及附肢的近远轴模式形成。Ft和Ds以优先异嗜性方式结合，并且Ds沿极性轴以不同模式表达。因此有人提出，Ft和Ds并非作为黏附分子，而是在一个了解甚少的信号通路中作为受体和配体发挥作用。为了验证这一假设，我们对Ft和Ds进行了结构功能分析，将它们的黏附功能和信号传导功能区分开来。我们发现，Ft的细胞外结构域对于其在生长、PCP和近远轴模式形成中的活性并非必需。因此，配体结合对于Ft的活性并非必要。相比之下，Ds的细胞外结构域对于介导其对PCP的影响是必要且充分的，这与Ds在PCP过程中作为配体发挥作用的模型一致。然而，我们也提供了证据表明，Ds可以独立于Ft调节生长，并且Ds的细胞内结构域可以影响近远轴模式形成，这两者都暗示了其独立于与Ft结合的功能。最后，我们表明，ft突变体或显性负性Ft构建体可以影响盘状结构生长，而不改变无翅基因（wingless）和无翅基因靶基因的表达。
