Department of Chemical and Biomolecular Engineering, North Carolina State University, Raleigh, NC 27695, USA.
Department of Chemical Engineering, Texas A&M University, College Station, TX 77843,USA.
Biol Open. 2024 Sep 15;13(9). doi: 10.1242/bio.061646. Epub 2024 Aug 29.
In developing tissues, morphogen gradients are thought to initialize gene expression patterns. However, the relationship between the dynamics of morphogen-encoded signals and gene expression decisions is largely unknown. Here we examine the dynamics of the Bone Morphogenetic Protein (BMP) pathway in Drosophila blastoderm-stage embryos. In this tissue, the BMP pathway is highly dynamic: it begins as a broad and weak signal on the dorsal half of the embryo, then 20-30 min later refines into a narrow, intense peak centered on the dorsal midline. This dynamical progression of the BMP signal raises questions of how it stably activates target genes. Therefore, we performed live imaging of the BMP signal and found that dorsal-lateral cells experience only a short transient in BMP signaling, after which the signal is lost completely. Moreover, we measured the transcriptional response of the BMP target gene pannier in live embryos and found it to remain activated in dorsal-lateral cells, even after the BMP signal is lost. Our findings may suggest that the BMP pathway activates a memory, or 'ratchet' mechanism that may sustain gene expression.
在发育组织中,形态发生素梯度被认为是基因表达模式的起始因素。然而,形态发生素编码信号的动态与基因表达决策之间的关系在很大程度上是未知的。在这里,我们研究了果蝇胚胎胚盘期的骨形态发生蛋白(BMP)途径的动态。在这个组织中,BMP 途径非常活跃:它最初在胚胎的背侧半形成一个广泛而微弱的信号,然后 20-30 分钟后,信号精细地集中在背中线。BMP 信号的这种动态进展引发了一个问题,即它如何稳定地激活靶基因。因此,我们对 BMP 信号进行了实时成像,发现背侧-外侧细胞只经历了短暂的 BMP 信号转导,之后信号完全丢失。此外,我们在活体胚胎中测量了 BMP 靶基因 pannier 的转录反应,发现即使 BMP 信号丢失后,pannier 在背侧-外侧细胞中仍保持激活。我们的研究结果可能表明,BMP 途径激活了一种记忆或“棘轮”机制,这种机制可能维持基因表达。