2009年6月3日,北京生命科学研究所张宏实验室在Developmental Biology上发表题为 “The temporally regulated transcription factor SEL-7 controls developmental timing in C. elegans” 的文章,该文章主要报道了线虫的sel-7基因在发育的时间调控过程中的作用。
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调控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。线虫的侧线细胞(seam cell)在不同的发言阶段具有不同的细胞分裂分化行为,是一个很好的模型而被广泛用于发育的时间调控的研究中。
本文报道了sel-7基因参与决定了线虫侧线细胞L3时期的细胞命运,sel-7的功能性缺失会导致侧线细胞L2的细胞命运在L3时期重复出现。sel-7之所以能调控细胞的命运是因为它调节了hbl-1的时间表达模式,而hbl-1是已知的一个参与L2/L3细胞命运转换的调控因子。sel-7是独立于其他异时性基因(lin-46, daf-12和let-7家族miRNA)来抑制L2的细胞命运的滞后表达的。sel-7基因本身在侧线细胞中的表达也是具有时间属性的,这种表达方式是由一段保守的位于sel-7基因内含子里的42bp的序列决定的。此外,作者还发现介导转录复合物参与sel-7基因的功能并由此影响侧线细胞的发育。本研究发现了一个新的受时间调控的基因sel-7能调控侧线细胞的L2/L3命运转换并证明了介导转录复合物也参与了线虫侧线细胞的时间信息的整合传递。
博士生夏丹为本文第一作者,论文的其他作者还有北京生命科学研究所的黄鑫欣。张宏博士为本文通讯作者。此项研究由科技部863计划,北京市科委资助,在北京生命科学研究所完成。
推荐原始出处:
Developmental Biology doi:10.1016/j.ydbio.2009.05.574
The temporally regulated transcription factor SEL-7 controls developmental timing in C. elegans
Dan Xiaa, Xinxin Huanga and Hong Zhang, a,
aNational Institute of Biological Sciences, No. 7 Science Park Road, Zhongguancun Life Science Park, Beijing, 102206, PR China
The temporal sequence of cell division and differentiation is explicitly controlled for succession and synchrony of developmental events. In this study we describe how the Caenorhabditis elegans gene sel-7 specifies the L3 stage-specific fate of seam cells, which adopt temporal specificities at each of four larval stages. Loss of function of sel-7 causes reiteration of the L2 stage fate at the L3 stage. sel-7 is involved in regulating the temporal expression pattern of hbl-1, which is a key factor in specifying the L2/L3 progression. We also show that sel-7 functions redundantly with other retarded heterochronic genes, including lin-46, daf-12 and the let-7 family miRNAs, in preventing adoption of the L2 fate at later stages. Expression of sel-7 in seam cells is temporally regulated through an evolutionarily conserved regulatory element located in intron 4 of sel-7. We further demonstrate that reiteration of the L2 proliferative seam cell division at the L3 stage in sel-7 mutants requires activity of the transcriptional mediator complex. Our study reveals that sel-7 functions as a novel heterochronic gene in controlling temporal cell identities and also demonstrates a role of the transcriptional mediator complex in integrating temporal information to specify seam cell division patterns in C. elegans.