Tbl3 regulates cell cycle length during zebrafish development.
Tbl3 regulates cell cycle length during zebrafish development.
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DOI：
10.1016/j.ydbio.2012.05.024
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发表时间：
2012-08-15
影响因子：
2.7
通讯作者：
Trede NS
中科院分区：
文献类型：
--
作者：
Hutchinson SA;Tooke-Locke E;Wang J;Tsai S;Katz T;Trede NS
细胞周期速率的调节对于发育过程中增殖和分化的正确时机至关重要。细胞周期速率的变化会对发育器官的大小，形状和细胞类型产生深远的影响。我们以前确定了一个斑马鱼突变锡兰（cey），有一个严重的减少T细胞和造血干/祖细胞（HSPCs）。我们发现cey表型是由于缺乏基因转导素（β）样3（tbl 3）。酵母中的tbl 3同源物通过维持rRNA水平和防止p53诱导的细胞死亡来调节细胞周期。斑马鱼tbl 3是母系表达的，但在发育后期，其表达仅限于特定组织。在cey突变体中表达tbl 3的组织严重减少，包括HSPC、视网膜、外分泌胰腺、肠和颌软骨。这些组织的规格是正常的，表明尺寸减小是由于分化细胞数量减少。Tbl 3 MO注射到野生型或p53-/-突变胚胎中表现为cey，表明tbl 3的缺失导致cey的特异性缺陷。由于细胞周期的减慢，造血和视网膜发育的进展在受精后3天开始延迟。与酵母相反，Tbl 3的减少导致细胞周期减慢，而没有p53诱导的细胞死亡的相应增加。这些数据表明，tbl 3在发育过程中发挥组织特异性调节细胞周期速率的作用。
The regulation of cell cycle rate is essential for the correct timing of proliferation and differentiation during development. Changes to cell cycle rate can have profound effects on the size, shape and cell types of a developing organ. We previously identified a zebrafish mutant ceylon (cey) that has a severe reduction in T cells and hematopoietic stem/progenitor cells (HSPCs). Here we find that the cey phenotype is due to absence of the gene transducin (beta)-like 3 (tbl3). The tbl3 homologue in yeast regulates the cell cycle by maintaining rRNA levels and preventing p53-induced cell death. Zebrafish tbl3 is maternally expressed, but later in development its expression is restricted to specific tissues. Tissues expressing tbl3 are severely reduced in cey mutants, including HSPCs, the retina, exocrine pancreas, intestine, and jaw cartilage. Specification of these tissues is normal, suggesting the reduced size is due to a reduced number of differentiated cells. Tbl3 MO injection into either wild-type or p53-/- mutant embryos phenocopies cey, indicating that loss of tbl3 causes specific defects in cey. Progression of both hematopoietic and retinal development is delayed beginning at 3 days post fertilization due to a slowing of the cell cycle. In contrast to yeast, reduction of Tbl3 causes a slowing of the cell cycle without a corresponding increase in p53 induced cell death. These data suggest that tbl3 plays a tissue-specific role regulating cell cycle rate during development.
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