Gallet A, Erkner A, Charroux B, Fasano L, Kerridge S
Laboratoire de Génétique et Physiologie du Développement UMR 9943 CNRS-Université IBDM CNRS-INSERM-Université de la Méditerranée Campus de Luminy Case 907, F-13288, Marseille, Cedex 09, France.
Curr Biol. 1998;8(16):893-902. doi: 10.1016/s0960-9822(07)00369-7.
One function of the Wingless signal cascade is to determine the 'naked' cuticle cell-fate choice instead of the denticled one in Drosophila larvae. Wingless stabilises cytoplasmic Armadillo, which may act in a transcriptional activator complex with the DNA-binding protein T-cell factor (also known as Pangolin). As these components are critical for all Wingless-dependent patterning events, the problem arises as to how specific outputs are achieved.
The Teashirt zinc finger protein was found to be necessary for a subset of late Wingless-dependent functions in the embryonic trunk segments where the teashirt gene is expressed. Teashirt was found to be required for the maintenance of the late Wingless signalling target gene wingless but not for an earlier one, engrailed. Armadillo and Teashirt proteins showed similar Wingless-dependent modulation patterns in homologous parts of each trunk segment in embryos, with high levels of nuclear Teashirt and intracellular Armadillo within cells destined to form naked cuticle. We found that Teashirt associates with, and requires, Armadillo in a complex for its function.
Teashirt binds to, and requires, Armadillo for the naked cell-fate choice in the larval trunk. Teashirt is required for trunk segment identity, suggesting that Teashirt provides a region-specific output to Armadillo activity. Further modulation of Wingless is achieved in homologous parts of each trunk segment where Wingless and Teashirt are especially active. Our results provide a novel, cell-intrinsic mechanism to explain the modulation of the activity of the Wingless signalling pathway.
无翅信号级联反应的一个功能是在果蝇幼虫中决定“裸露”表皮细胞的命运选择而非齿状表皮细胞的命运选择。无翅可使细胞质中的犰狳蛋白稳定,该蛋白可能与DNA结合蛋白T细胞因子(也称为穿山甲蛋白)在转录激活复合物中发挥作用。由于这些成分对所有依赖无翅的模式形成事件都至关重要,因此就出现了如何实现特定输出的问题。
在表达teashirt基因的胚胎躯干节段中,发现T恤锌指蛋白对于晚期依赖无翅的部分功能是必需的。发现T恤对于维持晚期无翅信号靶基因无翅是必需的,但对于早期的 engrailed基因则不是必需的。在胚胎每个躯干节段的同源部分,犰狳蛋白和T恤蛋白显示出相似的依赖无翅的调节模式,在注定形成裸露表皮的细胞内,细胞核中的T恤和细胞内的犰狳蛋白水平较高。我们发现T恤在一个复合物中与犰狳蛋白结合并需要它来发挥功能。
T恤在幼虫躯干中结合并需要犰狳蛋白来进行裸露细胞命运的选择。躯干节段的身份需要T恤,这表明T恤为犰狳蛋白活性提供了区域特异性输出。在每个躯干节段的同源部分实现了对无翅的进一步调节,在这些部分无翅和T恤特别活跃。我们的结果提供了一种新的细胞内在机制来解释无翅信号通路活性的调节。