2011年4月6日，我所張宏實(shí)驗(yàn)室在 Development 上發(fā)表題為“The zinc-finger protein SEA-2 regulates larval developmental timing and adult lifespan in C. elegans”的文章,，該文章主要報(bào)道了線蟲的sea-2基因在發(fā)育的時(shí)間調(diào)控過程和衰老調(diào)控中的作用,。
在多細(xì)胞生物體的發(fā)育過程中，各個(gè)細(xì)胞的分裂和分化的程序都離不開精密的時(shí)間調(diào)控,。在秀麗線蟲(Caenorhabditis elegans)中，人們已經(jīng)發(fā)現(xiàn)了一系列的異時(shí)性基因參與決定各個(gè)發(fā)育時(shí)期的細(xì)胞行為。之前的研究表明衰老過程是受基因調(diào)控,，但衰老過程是否也受發(fā)育時(shí)間程序的調(diào)控尚不清楚。
本文利用線蟲進(jìn)行遺傳篩選發(fā)現(xiàn)了sea-2基因參與調(diào)控線蟲側(cè)線細(xì)胞的增殖和分化,，這是通過控制發(fā)育時(shí)間通路來完成的,。在sea-2突變體中,，線蟲在第三幼蟲階段（L3）會繼續(xù)進(jìn)行增殖性細(xì)胞分裂而不是正常的不對稱細(xì)胞分裂。SEA-2編碼一個(gè)含有鋅指結(jié)構(gòu)域的蛋白,，我們證明sea-2是通過作用于它下游的靶基因lin-28來起作用的,，而且這種調(diào)控方式是在翻譯水平的調(diào)控。此外,，本研究還發(fā)現(xiàn)sea-2參與了劑量補(bǔ)償效應(yīng)通路和衰老調(diào)控通路并在其中發(fā)揮重要作用,，同時(shí)首次證明了衰老調(diào)控通路的基因daf-2和daf-16也參與發(fā)育的時(shí)間調(diào)控，本研究表明發(fā)育時(shí)間調(diào)控通路和衰老調(diào)控通路之間是會相互影響的,。
黃鑫欣為本文第一作者,，論文的其他作者還有本所研究生張慧。張宏博士為本文通訊作者,。此項(xiàng)研究由科技部973計(jì)劃,，北京市科委資助，在北京生命科學(xué)研究所完成,。（生物谷Bioon.com）
生物谷推薦原文出處：
Development doi: 10.1242/dev.057109
The zinc-finger protein SEA-2 regulates larval developmental timing and adult lifespan in C. elegans
Xinxin Huang, Hui Zhang and Hong Zhang*
Summary
Like other biological processes, aging is regulated by genetic pathways. However, it remains largely unknown whether aging is determined by an innate programmed timing mechanism and, if so, how this timer is linked to the mechanisms that control developmental timing. Here, we demonstrate that sea-2, which encodes a zinc-finger protein, controls developmental timing in C. elegans larvae by regulating expression of the heterochronic gene lin-28 at the post-transcriptional level. lin-28 is also essential for the autosomal signal element (ASE) function of sea-2 in X:A signal assessment. We also show that sea-2 modulates aging in adulthood. Loss of function of sea-2 slows the aging process and extends the adult lifespan in a DAF-16/FOXO-dependent manner. Mutation of sea-2 promotes nuclear translocation of DAF-16 and subsequent activation of daf-16 targets. We further demonstrate that insulin/IGF-1 signaling functions in the larval heterochronic circuit. Loss of function of the insulin/IGF-1 receptor gene daf-2, which extends lifespan, also greatly enhances the retarded heterochronic defects in sea-2 mutants. Regulation of developmental timing by daf-2 requires daf-16 activity. Our study provides evidence for intricate interplay between the heterochronic circuit that controls developmental timing in larvae and the timing mechanism that modulates aging in adults.
