果蝇成对盒基因Poxm的生物学功能及其转录调控的研究

Paired box(Pax) gene family encodes a set of evolutionally conserved transcription factors that play key roles in animal development,wound healing and tumorigenesis. Drosophila paired box gene Poxm and mammalian Pax1/9 belong to the same subgroup.We have demonstrated previouly that Pxom is a key gene during Drosophila somatic muscle development. Recently, we found that Poxm also play important roles in the development of esophagus,hindgut and testis. Homozygous Poxm mutant dies at early larval stage due to defected esophagus. The mutants partially rescued by transgenes of Poxm coding region combined with different cis-regulatory regions showed developmental defects in hindgut and testis. We plan to continue the investigation on specific biological functions of Poxm in the development of esophagus, hindgut and testis. In addtion, the transcriptional regulation of Poxm will be studied on the base of cis-regulatory elements. This investigation will provide animal models to study esophageal and large intestine cancers and male infertility.

成对盒（Paired box）基因家族编码一组在进化上非常保守的转录因子，在多细胞动物机体发育、损伤修复、肿瘤发生发展等生理病理过程中起关键的调控作用。果蝇成对盒基因Poxm与哺乳类的Pax1/9同属Pax基因的一个亚族。我们以前的工作显示Poxm是果蝇体壁肌肉发育中一个关键基因，最近我们发现其在食道、后肠及雄性生殖腺的发育中也具有非常重要的功能。Poxm基因敲除纯合突变体由于食道发育缺陷死于幼虫早期，我们将一系列含Poxm编码区及不同调控区的转基因杂交到Poxm基因敲除果蝇遗传背景中，不同Poxm部分回复的果蝇突变体分别显示了后肠与睾丸的功能缺陷。本申请将进一步研究Poxm在食道、后肠与睾丸发育中的具体功能，如影响的具体发育进程与靶基因。此外从Poxm调控区的顺式作用元件入手研究Poxm转录调控的分子机理。该研究可能为食道癌、大肠癌的发生与雄性不育提供相关动物模型及理论依据。