Hughes Samantha, Wilkinson Henry, Gilbert Sophie P R, Kishida Marcia, Ding Siyu Serena, Woollard Alison
Department of Biochemistry, University of Oxford, Oxford, United Kingdom.
PLoS One. 2014 Dec 10;9(12):e114998. doi: 10.1371/journal.pone.0114998. eCollection 2014.
Correct cell fate choice is crucial in development. In post-embryonic development of the hermaphroditic Caenorhabitis elegans, distinct cell fates must be adopted in two diverse tissues. In the germline, stem cells adopt one of three possible fates: mitotic cell cycle, or gamete formation via meiosis, producing either sperm or oocytes. In the epidermis, the stem cell-like seam cells divide asymmetrically, with the daughters taking on either a proliferative (seam) or differentiated (hypodermal or neuronal) fate. We have isolated a novel conserved C. elegans tetratricopeptide repeat containing protein, TRD-1, which is essential for cell fate determination in both the germline and the developing epidermis and has homologs in other species, including humans (TTC27). We show that trd-1(RNAi) and mutant animals have fewer seam cells as a result of inappropriate differentiation towards the hypodermal fate. In the germline, trd-1 RNAi results in a strong masculinization phenotype, as well as defects in the mitosis to meiosis switch. Our data suggests that trd-1 acts downstream of tra-2 but upstream of fem-3 in the germline sex determination pathway, and exhibits a constellation of phenotypes in common with other Mog (masculinization of germline) mutants. Thus, trd-1 is a new player in both the somatic and germline cell fate determination machinery, suggestive of a novel molecular connection between the development of these two diverse tissues.
正确的细胞命运选择在发育过程中至关重要。在雌雄同体的秀丽隐杆线虫的胚后发育中，两种不同的组织必须采用不同的细胞命运。在生殖系中，干细胞有三种可能的命运之一：有丝分裂细胞周期，或通过减数分裂形成配子，产生精子或卵子。在表皮中，类似干细胞的接缝细胞不对称分裂，子代细胞要么具有增殖性（接缝）命运，要么具有分化性（皮下或神经元）命运。我们分离出了一种新的保守的含有四肽重复序列的秀丽隐杆线虫蛋白TRD-1，它对于生殖系和发育中的表皮中的细胞命运决定至关重要，并且在包括人类（TTC27）在内的其他物种中具有同源物。我们发现，trd-1（RNAi）和突变动物由于向皮下命运的不适当分化而导致接缝细胞减少。在生殖系中，trd-1 RNAi导致强烈的雄性化表型，以及有丝分裂向减数分裂转换的缺陷。我们的数据表明，trd-1在生殖系性别决定途径中作用于tra-2的下游但在fem-3的上游，并表现出与其他Mog（生殖系雄性化）突变体共有的一系列表型。因此，trd-1是体细胞和生殖系细胞命运决定机制中的一个新成员，提示这两种不同组织的发育之间存在新的分子联系。
