Berardi Skyler, McFall Alanna, Toledo-Hernandez Amanda, Coote Carolyn, Graham Hillary, Stine Laurel, Rhodehouse Kyle, Auernhamer Anna, Van Wynsberghe Priscilla M
Department of Biology, Colgate University, Hamilton, NY 13346, USA.
Department of Biology, Colgate University, Hamilton, NY 13346, USA.
Mech Dev. 2018 Oct;153:42-53. doi: 10.1016/j.mod.2018.08.008. Epub 2018 Aug 23.
Germline stem cells are maintained in the distal region of the C. elegans gonad. These cells undergo mitotic divisions, and GLP-1/Notch signaling dictates whether they remain in this state. The somatic distal tip cell (DTC) caps the end of the distal gonad and is essential for maintenance of the germline mitotic zone. As germ cells move away from the DTC they exit mitosis and enter early meiotic prophase. Here we identify the Period protein homolog LIN-42 as a new regulator of germline development in C. elegans. LIN-42 is expressed in almost all somatic cells including the DTC, and LIN-42 functions as a transcription factor in the heterochronic pathway and to regulate molting. We found that the mitotic proliferative zone size in the distal gonad was significantly reduced by ~25% in lin-42 mutants compared to WT N2 worms. A lin-42 mutation also reduced the mitotic proliferative zone size caused by glp-1 partial loss-of-function and gain-of-function alleles. LIN-42 mediates this effect, at least in part, by regulating expression of the GLP-1/Notch ligand LAG-2. We further show that lin-42 expression itself is regulated by ATX-2, which promotes germline proliferation and is the homolog of the RNA binding protein ataxin-2 that is implicated in human neurodegenerative diseases. Altogether our results establish a new role for the conserved, important Period protein homolog LIN-42 in regulating early germline development. These results also suggest that in addition to regulating behavioral rhythms, the circadian clock plays an important role in communicating environmental signals to essential reproductive pathways.
生殖系干细胞维持在秀丽隐杆线虫性腺的远端区域。这些细胞进行有丝分裂，而GLP-1/Notch信号决定它们是否保持这种状态。体细胞远端顶端细胞（DTC）覆盖远端性腺的末端，对维持生殖系有丝分裂区至关重要。随着生殖细胞远离DTC，它们退出有丝分裂并进入减数分裂前期。在这里，我们鉴定出周期蛋白同源物LIN-42是秀丽隐杆线虫生殖系发育的一种新调节因子。LIN-42在几乎所有体细胞中表达，包括DTC，并且LIN-42在异时性途径中作为转录因子发挥作用并调节蜕皮。我们发现，与野生型N2蠕虫相比，lin-42突变体中远端性腺的有丝分裂增殖区大小显著减少了约25%。lin-42突变也减少了由glp-1部分功能丧失和功能获得等位基因引起的有丝分裂增殖区大小。LIN-42至少部分地通过调节GLP-1/Notch配体LAG-2的表达来介导这种效应。我们进一步表明，lin-42的表达本身受ATX-2调节，ATX-2促进生殖系增殖，并且是与人类神经退行性疾病有关的RNA结合蛋白ataxin-2的同源物。总之，我们的结果确立了保守且重要的周期蛋白同源物LIN-42在调节早期生殖系发育中的新作用。这些结果还表明，除了调节行为节律外，生物钟在将环境信号传递到基本生殖途径中也起着重要作用。
