Scapula development is governed by genetic interactions of Pbx1 with its family members and with Emx2 via their cooperative control of Alx1
Scapula development is governed by genetic interactions of Pbx1 with its family members and with Emx2 via their cooperative control of Alx1
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DOI：
10.1242/dev.048819
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发表时间：
2010-08-01
期刊：
影响因子：
4.6
通讯作者：
Zappavigna, Vincenzo
中科院分区：
文献类型：
--
作者：
Capellini, Terence D.;Vaccari, Giulia;Zappavigna, Vincenzo
肩胛骨发育的遗传途径在很大程度上是未知的，因为控制肢体形态发生的基因网络对肩胛骨形成的影响有限。对小鼠 Pbx 和 Emx2 基因突变体的分析表明它们在带状发育中的潜在作用。在这项研究中，通过产生复合突变小鼠，我们研究了Pbx基因对肩胛骨发育的遗传控制及其与Emx2的功能关系。 Pbx和Pbx1的分析； Emx2 复合突变体表明，Pbx 基因在肩部发育中具有重叠的功能，并且 Pbx1 在此过程中与 Emx2 存在遗传相互作用。在这里，我们提供了Pbx1的生化基础； Emx2 遗传相互作用表明 Pbx1 和 Emx2 可以作为异二聚体结合特定的 DNA 序列。此外，在这些突变体中，对肩胛骨发育至关重要的基因的表达发生了改变，表明Pbx基因在肩胛骨形成的重要途径的上游发挥作用。特别是，所有复合突变体中均不存在肩胛骨图案效应子 Alx1 的表达。我们证明 Pbx1 和 Emx2 在体内与 Alx1 上游的保守序列结合，并通过这个潜在的调控元件协同激活其转录。我们的结果确立了 Pbx1 在与其家族成员和 Emx2 的遗传相互作用中的重要作用，并描绘了肩带发育中的新型调控网络。
The genetic pathways underlying shoulder blade development are largely unknown, as gene networks controlling limb morphogenesis have limited influence on scapula formation. Analysis of mouse mutants for Pbx and Emx2 genes has suggested their potential roles in girdle development. In this study, by generating compound mutant mice, we examined the genetic control of scapula development by Pbx genes and their functional relationship with Emx2. Analyses of Pbx and Pbx1; Emx2 compound mutants revealed that Pbx genes share overlapping functions in shoulder development and that Pbx1 genetically interacts with Emx2 in this process. Here, we provide a biochemical basis for Pbx1; Emx2 genetic interaction by showing that Pbx1 and Emx2 can bind specific DNA sequences as heterodimers. Moreover, the expression of genes crucial for scapula development is altered in these mutants, indicating that Pbx genes act upstream of essential pathways for scapula formation. In particular, expression of Alx1, an effector of scapula blade patterning, is absent in all compound mutants. We demonstrate that Pbx1 and Emx2 bind in vivo to a conserved sequence upstream of Alx1 and cooperatively activate its transcription via this potential regulatory element. Our results establish an essential role for Pbx1 in genetic interactions with its family members and with Emx2 and delineate novel regulatory networks in shoulder girdle development.