Temporal remodeling of the cell cycle accompanies differentiation in the Drosophila germline.
Temporal remodeling of the cell cycle accompanies differentiation in the Drosophila germline.
复制标题
细胞周期的时间重塑伴随果蝇种系分化。
DOI：
10.1016/j.ydbio.2017.07.001
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发表时间：
2017-09-01
影响因子：
2.7
通讯作者：
Ables ET
中科院分区：
文献类型：
--
作者：
Hinnant TD;Alvarez AA;Ables ET
多细胞生物的发育依赖于细胞分化和增殖的协调调节。越来越多的证据表明，与细胞周期机制相关的一些分子调控途径也决定了细胞的命运;然而，细胞周期是如何与细胞分化一起重塑的，这在很大程度上仍不清楚。在果蝇卵子发生过程中，成熟的卵母细胞是通过一系列精确控制的分裂和分化步骤产生的，起源于单个组织特异性干细胞。此外，随着卵子发生的进行，生殖系干细胞（GSC）及其分化后代保持主要线性排列。在单个组织的背景下可视化逐步分化事件的能力使果蝇卵巢成为研究细胞周期重塑的特殊模型。为了描述生殖细胞在原位分化时细胞周期是如何重塑的，我们使用了果蝇荧光泛素细胞周期指示剂（Fly-FUCCI）系统，其中GFP：：E2 f1和RFP：：CycB的可降解版本在细胞周期的每个阶段荧光标记细胞。我们发现细胞周期的G1、S和G2期的长度在分化过程中发生了巨大变化，并将4/8细胞囊肿确定为细胞为专门细胞周期做准备的关键发育过渡状态。我们的数据表明，转录激活因子E2 f1，它控制从G1期到S期的过渡，是一个关键的有丝分裂在早期生殖细胞的调节器。我们的数据支持E2 f1是必要的适当的GSC增殖，自我更新和子细胞发育的模型。相比之下，虽然E2 f1降解的Cullin 4（Cul 4）-含有泛素E3连接酶（CRL 4）是必不可少的发育过渡在早期生殖系，我们的数据不支持E2 f1降解的作用作为一种机制，以限制GSC增殖或自我更新。总之，这些发现提供了对细胞增殖调节和分化细胞命运获得的进一步见解，对发育中的组织具有广泛的影响。
Development of multicellular organisms relies upon the coordinated regulation of cellular differentiation and proliferation. Growing evidence suggests that some molecular regulatory pathways associated with the cell cycle machinery also dictate cell fate; however, it remains largely unclear how the cell cycle is remodeled in concert with cell differentiation. During Drosophila oogenesis, mature oocytes are created through a series of precisely controlled division and differentiation steps, originating from a single tissue-specific stem cell. Further, germline stem cells (GSCs) and their differentiating progeny remain in a predominantly linear arrangement as oogenesis proceeds. The ability to visualize the stepwise events of differentiation within the context of a single tissue make the Drosophila ovary an exceptional model for study of cell cycle remodeling. To describe how the cell cycle is remodeled in germ cells as they differentiate in situ, we used the Drosophila Fluorescence Ubiquitin-based Cell Cycle Indicator (Fly-FUCCI) system, in which degradable versions of GFP::E2f1 and RFP::CycB fluorescently label cells in each phase of the cell cycle. We found that the lengths of the G1, S, and G2 phases of the cell cycle change dramatically over the course of differentiation, and identified the 4/8-cell cyst as a key developmental transition state in which cells prepare for specialized cell cycles. Our data suggest that the transcriptional activator E2f1, which controls the transition from G1 to S phase, is a key regulator of mitotic divisions in the early germline. Our data support the model that E2f1 is necessary for proper GSC proliferation, self-renewal, and daughter cell development. In contrast, while E2f1 degradation by the Cullin 4 (Cul4)-containing ubiquitin E3 ligase (CRL4) is essential for developmental transitions in the early germline, our data do not support a role for E2f1 degradation as a mechanism to limit GSC proliferation or self-renewal. Taken together, these findings provide further insight into the regulation of cell proliferation and the acquisition of differentiated cell fate, with broad implications across developing tissues.
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影响因子：
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通讯作者：
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