2011年4月6日，我所张宏实验室在 Development 上发表题为“The zinc-finger protein SEA-2 regulates larval developmental timing and adult lifespan in C. elegans”的文章，该文章主要报道了线虫的sea-2基因在发育的时间调控过程和衰老调控中的作用。
在多细胞生物体的发育过程中，各个细胞的分裂和分化的程序都离不开精密的时间调控。在秀丽线虫(Caenorhabditis elegans)中，人们已经发现了一系列的异时性基因参与决定各个发育时期的细胞行为。之前的研究表明衰老过程是受基因调控，但衰老过程是否也受发育时间程序的调控尚不清楚。
本文利用线虫进行遗传筛选发现了sea-2基因参与调控线虫侧线细胞的增殖和分化，这是通过控制发育时间通路来完成的。在sea-2突变体中，线虫在第三幼虫阶段（L3）会继续进行增殖性细胞分裂而不是正常的不对称细胞分裂。SEA-2编码一个含有锌指结构域的蛋白，我们证明sea-2是通过作用于它下游的靶基因lin-28来起作用的，而且这种调控方式是在翻译水平的调控。此外，本研究还发现sea-2参与了剂量补偿效应通路和衰老调控通路并在其中发挥重要作用，同时首次证明了衰老调控通路的基因daf-2和daf-16也参与发育的时间调控，本研究表明发育时间调控通路和衰老调控通路之间是会相互影响的。
黄鑫欣为本文第一作者，论文的其他作者还有本所研究生张慧。张宏博士为本文通讯作者。此项研究由科技部973计划，北京市科委资助，在北京生命科学研究所完成。（生物谷Bioon.com）
生物谷推荐原文出处：
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.
