Synergistic regulation of vertebrate muscle development by Dach2, Eya2, and Six1, homologs of genes required for Drosophila eye formation
Synergistic regulation of vertebrate muscle development by Dach2, Eya2, and Six1, homologs of genes required for Drosophila eye formation
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DOI：
10.1101/gad.13.24.3231
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发表时间：
1999-12-15
影响因子：
10.5
通讯作者：
Tabin, CJ
中科院分区：
文献类型：
--
作者：
Heanue, TA;Reshef, R;Tabin, CJ
我们已经鉴定出一种新的与果蝇基因同源的脊椎动物腊肠，腊肠2 （Dachshund2）。Dach2在发育中的小体中表达比任何与Pax3基因表达谱相似的肌源性基因都要早，Pax3基因先前被证明可以诱导肌肉分化。Pax3和Dach2参与了一个积极的调节反馈回路，类似于果蝇中Pax基因（Pax6同源物）和果蝇达克斯猎犬基因之间的反馈回路。虽然Dach2单独不能诱导肌发生，但Dach2可以与Eya2（一种与果蝇基因同源的脊椎动物基因，眼睛缺失）协同调节肌发生分化。此外，Eya2还可以与Six1（果蝇眼肌基因的脊椎动物同源基因）协同调节肌肉发生。Dach2与Eya2和Eya2与Six1对肌肉发育的协同调节与眼缺失和眼缺失的腊肠犬对果蝇眼睛形成的协同调节相似。这种协同调节可以通过Dach2和Eya2、Eya2和Six1蛋白之间的直接物理相互作用来解释，类似于果蝇蛋白之间的相互作用。本研究揭示了体细胞肌生成规范过程中一个新的调控层。此外，我们表明Pax， Dach， Eya和Six遗传网络在物种间是保守的。然而，这种遗传网络已被用于一种新的发育背景，即肌肉发生而不是眼睛发育，并已扩展到包括不直接同源的基因家族成员，例如Pax3而不是Pax6。
We have identified a novel vertebrate homolog of the Drosophila gene dachshund, Dachshund2 (Dach2). Dach2 is expressed in the developing somite prior to any myogenic genes with an expression profile similar to Pax3, a gene previously shown to induce muscle differentiation. Pax3 and Dach2 participate in a positive regulatory feedback loop, analogous to a feedback loop that exists in Drosophila between the Pax gene eyeless (a Pax6 homolog) and the Drosophila dachshund gene. Although Dach2 alone is unable to induce myogenesis, Dach2 can synergize with Eya2 (a vertebrate homolog of the Drosophila gene eyes absent) to regulate myogenic differentiation. Moreover, Eya2 can also synergize with Six1 (a vertebrate homolog of the Drosophila gene sine oculis) to regulate myogenesis. This synergistic regulation of muscle development by Dach2 with Eya2 and Eya2 with Six1 parallels the synergistic regulation of Drosophila eye formation by dachshund with eyes absent and eyes absent with sine oculis. This synergistic regulation is explained by direct physical interactions between Dach2 and Eya2, and Eya2 and Six1 proteins, analogous to interactions observed between the Drosophila proteins. This study reveals a new layer of regulation in the process of myogenic specification in the somites. Moreover, we show that the Pax, Dach, Eya, and Six genetic network has been conserved across species. However, this genetic network has been used in a novel developmental context, myogenesis rather than eye development, and has been expanded to include gene family members that are not directly homologous, for example Pax3 instead of Pax6.