Noise in the Vertebrate Segmentation Clock Is Boosted by Time Delays but Tamed by Notch Signaling.
Noise in the Vertebrate Segmentation Clock Is Boosted by Time Delays but Tamed by Notch Signaling.
复制标题
DOI：
10.1016/j.celrep.2018.04.069
复制
发表时间：
2018-05-15
期刊：
影响因子：
8.8
通讯作者：
Özbudak EM
中科院分区：
文献类型：
--
作者：
Keskin S;Devakanmalai GS;Kwon SB;Vu HT;Hong Q;Lee YY;Soltani M;Singh A;Ay A;Özbudak EM
驯服基因表达的细胞间变异性对于胚胎发育期间精确的模式形成至关重要。为了研究表达变异的来源和缓冲机制，我们研究了生物钟，脊椎动物分割时钟，控制脊柱的精确时空模式。通过计算斑马鱼中分段时钟基因的单个转录本，我们发现时钟基因具有低RNA幅度，并且表达变异性主要由基因外源性来源驱动，其被Notch信号抑制。我们进一步表明，表达噪音令人惊讶地增加，从后祖细胞区到前分割和分化区。我们的计算模型再现空间噪声配置文件，将空间增加基因表达的时间延迟。我们的研究结果表明，表达变异性是由脊椎动物组织中的时间延迟和细胞信号传导的平衡控制的，这将揭示多细胞系统中自然时钟的准确性，并激发工程师对强大的合成振荡器的研究。凯斯金等人表明，分段时钟转录水平显示出低幅度和高异质性。时钟基因表达变异性主要由基因外源性来源驱动，其被Notch信号转导抑制。基因表达噪音沿着后前轴增加。时间延迟的空间梯度对沿着轴的噪声梯度有贡献。
Taming cell-to-cell variability in gene expression is critical for precise pattern formation during embryonic development. To investigate the source and buffering mechanism of expression variability, we studied a biological clock, the vertebrate segmentation clock, controlling the precise spatiotemporal patterning of the vertebral column. By counting single transcripts of segmentation clock genes in zebrafish, we show that clock genes have low RNA amplitudes and expression variability is primarily driven by gene extrinsic sources, which is suppressed by Notch signaling. We further show that expression noise surprisingly increases from the posterior progenitor zone to the anterior segmentation and differentiation zone. Our computational model reproduces the spatial noise profile by incorporating spatially increasing time delays in gene expression. Our results, suggesting that expression variability is controlled by the balance of time delays and cell signaling in a vertebrate tissue, will shed light on the accuracy of natural clocks in multi-cellular systems and inspire engineering of robust synthetic oscillators. Keskin et al. show that segmentation clock transcription levels display low amplitude and high heterogeneity. Clock gene expression variability is primarily driven by gene extrinsic sources, which is suppressed by Notch signaling. Gene expression noise increases along the posteroanterior axis. Spatial gradients of time delays contribute to the noise gradient along the axis.
登录
查看更多内容
影响因子：
4.3
作者：
Jenkins RP;Hanisch A;Soza-Ried C;Sahai E;Lewis J
通讯作者：
Lewis J
影响因子：
30.8
作者：
Becskei, A;Kaufmann, BB;van Oudenaarden, A
通讯作者：
van Oudenaarden, A
影响因子：
4.6
作者：
Ay, Ahmet;Holland, Jack;Oezbudak, Ertugrul M.
通讯作者：
Oezbudak, Ertugrul M.
影响因子：
64.5
作者：
Ji, Ni;Middelkoop, Teije C.;van Oudenaarden, Alexander
通讯作者：
van Oudenaarden, Alexander
影响因子：
64.8
作者：
Jiang, YJ;Aerne, BL;Lewis, J
通讯作者：
Lewis, J