Systems Biology of Development Group, Friedrich Miescher Laboratory of the Max Planck Society, Tübingen, Germany.
Modeling Tumorigenesis Group, Translational Oncology Division, Eberhard Karls University Tübingen, Tübingen, Germany.
Elife. 2020 Nov 11;9:e58641. doi: 10.7554/eLife.58641.
Signaling molecules activate distinct patterns of gene expression to coordinate embryogenesis, but how spatiotemporal expression diversity is generated is an open question. In zebrafish, a BMP signaling gradient patterns the dorsal-ventral axis. We systematically identified target genes responding to BMP and found that they have diverse spatiotemporal expression patterns. Transcriptional responses to optogenetically delivered high- and low-amplitude BMP signaling pulses indicate that spatiotemporal expression is not fully defined by different BMP signaling activation thresholds. Additionally, we observed negligible correlations between spatiotemporal expression and transcription kinetics for the majority of analyzed genes in response to BMP signaling pulses. In contrast, spatial differences between BMP target genes largely collapsed when FGF and Nodal signaling were inhibited. Our results suggest that, similar to other patterning systems, combinatorial signaling is likely to be a major driver of spatial diversity in BMP-dependent gene expression in zebrafish.
信号分子激活不同的基因表达模式来协调胚胎发生,但时空表达多样性是如何产生的,这是一个悬而未决的问题。在斑马鱼中,BMP 信号梯度模式化了背腹轴。我们系统地鉴定了响应 BMP 的靶基因,发现它们具有不同的时空表达模式。光遗传学传递的高幅度和低幅度 BMP 信号脉冲的转录反应表明,时空表达不是由不同的 BMP 信号激活阈值完全定义的。此外,我们观察到,在响应 BMP 信号脉冲时,大多数分析基因的时空表达与转录动力学之间几乎没有相关性。相比之下,当抑制 FGF 和 Nodal 信号时,BMP 靶基因之间的空间差异大大减少。我们的结果表明,与其他模式系统类似,组合信号可能是斑马鱼中 BMP 依赖的基因表达中空间多样性的主要驱动因素。