2007年10月24日,，北京生命科學(xué)研究所張宏實(shí)驗(yàn)室在Genetics雜志上發(fā)表了題為“The Flightless I Homolog, fli-1, Regulates Anterior/Posterior Polarity, Asymmetric Cell Division and Ovulation During Caenorhabditis elegans Development” 的文章。該文章報(bào)道了Fli同源基因在線蟲發(fā)育過(guò)程中對(duì)肌動(dòng)蛋白依賴的生理過(guò)程的調(diào)控作用,。
Flightless I (Fli I) 是gelsolin家族中進(jìn)化上保守的蛋白,，它在體外具有對(duì)肌動(dòng)蛋白結(jié)合和切割的活性，但是Fli I在動(dòng)物發(fā)育過(guò)程中的生理學(xué)功能還很不清楚,?！ ?/p>
由我所張宏研究員所領(lǐng)導(dǎo)的課題組運(yùn)用遺傳學(xué)、分子生物學(xué),、免疫組織化學(xué)等實(shí)驗(yàn)方法克隆了線蟲fli-1基因并研究了它在肌動(dòng)蛋白介導(dǎo)的收縮性運(yùn)動(dòng)過(guò)程中的作用,。他們首先克隆了線蟲fli-1的同源基因，并發(fā)現(xiàn)它參與了對(duì)受精卵不對(duì)稱分裂和前后極性建立的調(diào)控,。同時(shí)他們還發(fā)現(xiàn)fli-1基因調(diào)控了體細(xì)胞的胞漿移動(dòng)和生殖細(xì)胞的發(fā)育,；并且在可以和磷酸肌糖途徑相互作用調(diào)節(jié)線蟲的排卵過(guò)程。他們通過(guò)對(duì)fli-1報(bào)告基因的觀察發(fā)現(xiàn)FLI-1主要分布在富含肌動(dòng)蛋白的區(qū)域,，而且在fli-1突變體的許多組織中肌動(dòng)蛋白細(xì)胞骨架是異常的,。最后他們還發(fā)現(xiàn)果蠅Fli I可以替代線蟲fli-1的功能。
這一研究對(duì)于了解哺乳動(dòng)物中與Fli I功能缺失相關(guān)疾病的病理有較大的提示作用,，同時(shí)也為研究gelsolin家族在動(dòng)物發(fā)育尤其是早期胚胎發(fā)育和肌肉發(fā)生中的生理學(xué)功能提供了重要的線索,。
博士生鄧寒松為本文第一作者，論文的其他作者還有本所的夏丹和方彬,。張宏博士為本文通訊作者,。此項(xiàng)研究由科技部863計(jì)劃，北京市科委資助,，在北京生命科學(xué)研究所完成,。（北京生命科學(xué)研究所）
原始出處:
Originally published as Genetics Published Articles Ahead of Print on August 24, 2007.
Genetics, Vol. 177, 847-860, October 2007, Copyright © 2007
doi:10.1534/genetics.107.078964
The Flightless I Homolog, fli-1, Regulates Anterior/Posterior Polarity, Asymmetric Cell Division and Ovulation During Caenorhabditis elegans Development
Hansong Deng*,, Dan Xia*,, Bin Fang and Hong Zhang,1
* Graduate Program, Peking union Medical College and Chinese Academy of Medical Sciences, Beijing 100730, People's Republic of China and National Institute of Biological Sciences, Beijing 102206, People's Republic of China
1 Corresponding author: National Institute of Biological Sciences, 7 Science Park Rd., Zhongguancun Life Science Park, Beijing 102206, People's Republic of China.
E-mail: [email protected]
Flightless I (Fli I) is an evolutionarily conserved member of the gelsolin family, containing actin-binding and severing activity in vitro. The physiological function of Fli I during animal development remains largely undefined. In this study, we reveal a key role of the Caenorhabditis elegans Fli I homolog, fli-1, in specifying asymmetric cell division and in establishing anterior–posterior polarity in the zygote. The fli-1 gene also regulates the cytokinesis of somatic cells and the development of germline and interacts with the phosphoinositol-signaling pathway in the regulation of ovulation. The fli-1 reporter gene shows that the localization of FLI-1 coincides with actin-rich regions and that the actin cytoskeleton is impaired in many tissues in the fli-1 mutants. Furthermore, the function of fli-1 in C. elegans can be functionally substituted by the Drosophila Fli I. Our studies demonstrate that fli-1 plays an important role in regulating the actin-dependent events during C. elegans development.
