Non-redundant selector and growth-promoting functions of two sister genes, buttonhead and Sp1, in Drosophila leg development.

Non-redundant selector and growth-promoting functions of two sister genes, buttonhead and Sp1, in Drosophila leg development.
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DOI:
10.1371/journal.pgen.1001001
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发表时间:
2010-06-24
期刊:
影响因子:
4.5
通讯作者:
Mann RS
Mann RS
中科院分区:
生物学2区
文献类型:
--
作者:
Estella C;Mann RS

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节肢动物和四足动物腿的形态截然不同,这表明这些附肢并不具有共同的进化起源。然而,尽管在形态上存在显著差异,但一段时间以来已知由Distalless(Dll)/Dlx基因家族编码的转录因子在两种结构的发育中起关键作用。在这里,我们表明,由Sp 8基因家族编码的第二个转录因子家族,以前牵连在脊椎动物肢体发育,也在节肢动物腿的发展中发挥了早期和根本性的作用。通过同时删除两个Sp 8的直系同源,buttonhead(btd)和Sp1,在果蝇胚胎发育的功能,我们发现,成年腿的发展是完全废除。值得注意的是,在没有这些因素的情况下,观察到从腹侧到背侧附属物身份的转换,这表明当腹侧命运被消除时,成年人的背侧命运变得去抑制。此外,我们表明,SP1起着更重要的作用,在腹侧附属物规格比btd和SP1位于遗传上游的Dll。除了这些选择子样基因功能,Sp1和btd也需要在幼虫阶段的腿的生长。脊椎动物Sp 8可以拯救果蝇基因的许多功能,尽管经过5亿多年的独立进化,这些活动仍然被保留下来。这些观察结果表明,一个古老的Sp 8/Dlx基因盒被用于在早期后生动物的原始肢状生长,这个盒子被增选多次在多个动物门的附属物形成。脊椎动物和无脊椎动物附肢的发育在许多方面不同。然而,尽管存在这些差异,与果蝇的Distalless(Dll)基因相关的基因(脊椎动物Dlx基因)对于多个动物门中的附属物的发育是重要的。这些发现提出了一个问题:不同的动物附肢是否有一个共同的进化起源。在脊椎动物中,与果蝇Sp1相关的第二个基因家族也在附肢发育中起着重要作用。虽然有一些证据表明Sp1家族成员可能在果蝇附肢发育中发挥作用,但缺乏确切的数据。使用一个新的缺陷,删除果蝇的姐妹基因,Sp1和buttonhead(btd),我们毫不含糊地评估它们在果蝇发育中的作用。我们发现,Sp1,但不是btd,是至关重要的指定腿(腹侧)的发展,这两个基因是必需的翅膀(背侧)的发展。我们还表明,Sp1位于Dll的遗传上游。Sp1和Dlx基因家族都用于脊椎动物和无脊椎动物的附肢发育,这一事实提供了惊人的证据,表明Sp1-Dlx关系代表了一个古老的基因网络,该网络用于共同祖先的附肢样生长。
The radically distinct morphologies of arthropod and tetrapod legs argue that these appendages do not share a common evolutionary origin. Yet, despite dramatic differences in morphology, it has been known for some time that transcription factors encoded by the Distalless (Dll)/Dlx gene family play a critical role in the development of both structures. Here we show that a second transcription factor family encoded by the Sp8 gene family, previously implicated in vertebrate limb development, also plays an early and fundamental role in arthropod leg development. By simultaneously removing the function of two Sp8 orthologs, buttonhead (btd) and Sp1, during Drosophila embryogenesis, we find that adult leg development is completely abolished. Remarkably, in the absence of these factors, transformations from ventral to dorsal appendage identities are observed, suggesting that adult dorsal fates become derepressed when ventral fates are eliminated. Further, we show that Sp1 plays a much more important role in ventral appendage specification than btd and that Sp1 lies genetically upstream of Dll. In addition to these selector-like gene functions, Sp1 and btd are also required during larval stages for the growth of the leg. Vertebrate Sp8 can rescue many of the functions of the Drosophila genes, arguing that these activities have been conserved, despite more than 500 million years of independent evolution. These observations suggest that an ancient Sp8/Dlx gene cassette was used in an early metazoan for primitive limb-like outgrowths and that this cassette was co-opted multiple times for appendage formation in multiple animal phyla. The development of vertebrate and invertebrate appendages differs in many respects. Yet, despite these differences, genes related to the Distalless (Dll) gene of Drosophila (vertebrate Dlx genes) are important for the development of appendages in multiple animal phyla. Such findings raise the question of whether disparate animal appendages have a common evolutionary origin. In vertebrates, a second gene family, related to Drosophila Sp1, also plays a fundamental role in appendage development. Although there was some evidence to suggest that Sp1 family members may play a role in Drosophila appendage development, definitive data were lacking. Using a new deficiency that removes both Drosophila sister genes, Sp1 and buttonhead (btd), we unambiguously assess their role in Drosophila development. We find that Sp1, but not btd, is critical for specifying leg (ventral) development, and that neither gene is required for wing (dorsal) development. We also show that Sp1 lies genetically upstream of Dll. The fact that both Sp1 and Dlx gene families are used for appendage development in vertebrates and invertebrates provides striking evidence that the Sp1–Dlx relationship represents an ancient gene network that was used in a common ancestor for appendage-like outgrowths.
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