Bender Aaron M, Wells Orion, Fay David S
Department of Molecular Biology, College of Agriculture, University of Wyoming, Dept. 3944, Laramie, WY 82071, USA.
Dev Biol. 2004 Sep 15;273(2):335-49. doi: 10.1016/j.ydbio.2004.06.009.
In screens for genetic modifiers of lin-35/Rb, the C. elegans retinoblastoma protein (Rb) homolog, we have identified a mutation in xnp-1. Mutations in xnp-1, including a presumed null allele, are viable and, in general, appear indistinguishable from the wild type. In contrast, xnp-1 lin-35 double mutants are typically sterile and exhibit severe defects in gonadal development. Analyses of the abnormal gonads indicate a defect in the lineages that generate cells of the sheath and spermatheca. xnp-1 encodes the C. elegans homolog of ATR-X, a human disease gene associated with severe forms of mental retardation and urogenital developmental defects. xnp-1/ATR-X is a member of the Swi2/Snf2 family of ATP-dependent DEAD/DEAH box helicases, which function in nucleosome remodeling and transcriptional regulation. Expression of an xnp-1 Colon, two colons GFP promoter fusion is detected throughout C. elegans development in several cell types including neurons and cells of the somatic gonad. Our findings demonstrate a new biological role for Rb family members in somatic gonad development and implicate lin-35 in the execution of multiple cell fates in C. elegans. In addition, our results suggest a possible conserved function for xnp-1/ATR-X in gonadal development across species.
在对秀丽隐杆线虫视网膜母细胞瘤蛋白(Rb)同源物lin-35/Rb的遗传修饰因子进行筛选时,我们在xnp-1中发现了一个突变。xnp-1中的突变,包括一个假定的无效等位基因,都是可行的,并且一般来说,与野生型没有明显区别。相比之下,xnp-1 lin-35双突变体通常是不育的,并且在性腺发育中表现出严重缺陷。对异常性腺的分析表明,在产生鞘细胞和受精囊细胞的谱系中存在缺陷。xnp-1编码ATR-X的秀丽隐杆线虫同源物,ATR-X是一种与严重智力迟钝和泌尿生殖系统发育缺陷相关的人类疾病基因。xnp-1/ATR-X是Swi2/Snf2家族中依赖ATP的DEAD/DEAH盒解旋酶的成员,其在核小体重塑和转录调控中发挥作用。在秀丽隐杆线虫发育过程中,在包括神经元和体细胞性腺细胞在内的几种细胞类型中都检测到了xnp-1::GFP启动子融合蛋白的表达。我们的研究结果证明了Rb家族成员在体细胞性腺发育中的新生物学作用,并表明lin-35参与了秀丽隐杆线虫多种细胞命运的执行。此外,我们的结果表明xnp-1/ATR-X在跨物种性腺发育中可能具有保守功能。