Lack of In Vivo Functional Compensation Between Pax Family Groups II and III in Rodents
Lack of In Vivo Functional Compensation Between Pax Family Groups II and III in Rodents
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DOI：
10.1093/molbev/msr114
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发表时间：
2011-10-01
影响因子：
10.7
通讯作者：
Relaix, Frederic
中科院分区：
文献类型：
--
作者：
Hayashi, Shinichiro;Rocancourt, Didier;Relaix, Frederic
Pax基因编码进化上保守的转录因子，在胚胎发育和器官发生中起关键作用。根据配对结构域、八肽基序和部分或全部同源结构域的存在，Pax蛋白被细分为四个亚家族：I （pax1和9）、II （Pax2、5和8）、III （Pax3和7）和IV （Pax4和6）。对该基因家族的进化研究尚不完整。然而，众所周知，每个家族都是通过复制四个相应的祖先基因进化而来的。Pax基因功能已被证明在亚群中是保守的。然而，尚不清楚是否有任何（早期）保守功能在亚群之间共享。为了研究II亚家族和III亚家族之间的保守功能，我们在小鼠中通过基因靶向用pax8编码序列替换了Pax3的等位基因。纯合子Pax3（Pax8/Pax8）胚胎表现出与Pax3缺陷突变胚胎难以区分的表型，具有神经管闭合缺陷，主干神经嵴细胞缺陷，骨骼肌缺陷，包括缺乏远程迁移的肌源性祖细胞和体发育受损。有趣的是，尽管Pax8在神经管中的表达位于Pax3的腹侧区域，但Pax8不能取代Pax3在神经管背侧的功能。总之，我们的研究结果表明，Pax8的表达不能补偿Pax3的缺陷，这表明在小鼠胚胎中Pax基因的一个亚家族与另一个亚家族之间缺乏功能补偿。我们的研究结果表明，Pax3/7和Pax2/5/8的功能是在祖先Pax基因复制后独立进化的。
Pax genes encode evolutionarily conserved transcription factors that play critical roles in embryonic development and organogenesis. Pax proteins are subdivided into four subfamilies: group I (Pax1and 9), II (Pax2, 5, and 8), III (Pax3 and 7), and IV (Pax4 and 6), based on the presence of a paired domain, an octapeptide motif and part or all of the homeodomain. Studies of the evolution of this gene family are incomplete. Nevertheless, it is known that each family evolved via duplication from four corresponding ancestral genes. Pax gene functions have been shown to be conserved within subgroups. It remains unclear, however, whether any (early) conserved function is shared between subgroups. To investigate conserved functions between subfamily II and III, we replaced an allele of Pax3 with a Pax8-coding sequence via gene targeting in the mouse. Homozygote Pax3(Pax8/Pax8) embryos display phenotypes indistinguishable from Pax3-deficient mutant embryos, with neural tube closure defects, a deficit in neural crest cells in the trunk, and skeletal muscle defects including absence of long-range migratory myogenic progenitors and impaired somite development. Interestingly, despite Pax8 expression in the neural tube in a domain ventral to that of Pax3, Pax8 cannot replace Pax3 function in the dorsal neural tube. Altogether, our results demonstrate that expression of Pax8 fails to compensate for Pax3 deficiency, demonstrating the absence of functional compensation between one subfamily of Pax genes and another in the mouse embryo. Our result suggests that Pax3/7 and Pax2/5/8 functions evolved independently after duplication of the ancestral progenitor Pax genes.