Differential roles of TGIF family genes in mammalian reproduction.
Differential roles of TGIF family genes in mammalian reproduction.
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DOI：
10.1186/1471-213x-11-58
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发表时间：
2011-09-29
影响因子：
--
通讯作者：
Pask AJ
中科院分区：
文献类型：
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作者：
Hu Y;Yu H;Shaw G;Renfree MB;Pask AJ
TG相互作用因子（TG interacting factors，TGIFs）属于TALE同源结构域蛋白家族，在人类中包括TGIF 1、TGIF 2和TGIFLX/Y。TGIF 1和TGIF 2均作为抑制TGF-β信号传导的转录因子。人TGIFLX及其直系同源物小鼠中的Tex 1是仅在成年睾丸中表达的X连锁基因。TGIF 2通过复制从TGIF 1产生，而TGIFLX通过反转录转座到X染色体产生。这些基因尚未在任何非真兽目哺乳动物中得到表征。因此，我们研究了TGIF家族在tammar小袋鼠（一种有袋类哺乳动物），以调查他们在生殖中的作用，以及如何以及何时这些基因可能已经进化出它们的功能和染色体位置。TGIF 1和TGIF 2都存在于常染色体上的tammar基因组中，但TGIFLX不存在。Tammar TGIF 1在胚胎发生、性分化和成体组织中的表达模式与真兽目哺乳动物中的TGIF 1相似，表明其功能保守。Tammar TGIF 2在人类和小鼠的早期发育中普遍表达，但在成人中，它仅在性腺和脾脏中表达，更像人类TGIFLX和小鼠Tex 1的表达模式。Tammar TGIF 2 mRNA在圆形和细长精子细胞中特异性检测到。成熟精子中未检测到mRNA。TGIF 2蛋白特异性定位于精子细胞的胞质、成熟精子尾部的残体和中段。这些数据表明tammar TGIF 2可能参与精子发生，就像真兽目动物中的TGIFLX一样。首次在卵巢中检测到TGIF 2，其mRNA在颗粒细胞和卵泡膜细胞中产生，这表明它也可能在卵泡发生中发挥作用。tammar TGIF 2在真兽目动物中与X连锁旁系同源物的限制性和非常相似的表达表明，TGIF 1，TGIF 2和TGIFLX在真兽目动物中的进化伴随着从普遍存在到组织特异性表达的变化。TGIF 2在tammar成体性腺中的分布和定位表明，TGIF家族在生育力中具有超保守的功能，并且TGIF 2在其反转录转座到真兽目哺乳动物的X染色体之前很久就已经在精子发生和潜在的卵泡发生中起作用。这些结果也提供了进一步的证据，真兽X染色体积极招募性和生殖相关的基因在哺乳动物的进化。
TG-interacting factors (TGIFs) belong to a family of TALE-homeodomain proteins including TGIF1, TGIF2 and TGIFLX/Y in human. Both TGIF1 and TGIF2 act as transcription factors repressing TGF-β signalling. Human TGIFLX and its orthologue, Tex1 in the mouse, are X-linked genes that are only expressed in the adult testis. TGIF2 arose from TGIF1 by duplication, whereas TGIFLX arose by retrotransposition to the X-chromosome. These genes have not been characterised in any non-eutherian mammals. We therefore studied the TGIF family in the tammar wallaby (a marsupial mammal) to investigate their roles in reproduction and how and when these genes may have evolved their functions and chromosomal locations. Both TGIF1 and TGIF2 were present in the tammar genome on autosomes but TGIFLX was absent. Tammar TGIF1 shared a similar expression pattern during embryogenesis, sexual differentiation and in adult tissues to that of TGIF1 in eutherian mammals, suggesting it has been functionally conserved. Tammar TGIF2 was ubiquitously expressed throughout early development as in the human and mouse, but in the adult, it was expressed only in the gonads and spleen, more like the expression pattern of human TGIFLX and mouse Tex1. Tammar TGIF2 mRNA was specifically detected in round and elongated spermatids. There was no mRNA detected in mature spermatozoa. TGIF2 protein was specifically located in the cytoplasm of spermatids, and in the residual body and the mid-piece of the mature sperm tail. These data suggest that tammar TGIF2 may participate in spermiogenesis, like TGIFLX does in eutherians. TGIF2 was detected for the first time in the ovary with mRNA produced in the granulosa and theca cells, suggesting it may also play a role in folliculogenesis. The restricted and very similar expression of tammar TGIF2 to X-linked paralogues in eutherians suggests that the evolution of TGIF1, TGIF2 and TGIFLX in eutherians was accompanied by a change from ubiquitous to tissue-specific expression. The distribution and localization of TGIF2 in tammar adult gonads suggest that there has been an ultra-conserved function for the TGIF family in fertility and that TGIF2 already functioned in spermatogenesis and potentially folliculogenesis long before its retrotransposition to the X-chromosome of eutherian mammals. These results also provide further evidence that the eutherian X-chromosome has actively recruited sex and reproductive-related genes during mammalian evolution.