Department of Biology, Georgia Southern University, Statesboro, GA, 30460, USA.
Morphism Institute, Seattle, WA, 98117, USA.
Sci Rep. 2020 Apr 30;10(1):7370. doi: 10.1038/s41598-020-64247-2.
Living organisms require complex signaling interactions and proper regulation of these interactions to influence biological processes. Of these complex networks, one of the most distinguished is the Notch pathway. Dysregulation of this pathway often results in defects during organismal development and can be a causative mechanism for initiation and progression of cancer. Despite previous research entailing the importance of this signaling pathway and the organismal processes that it is involved in, less is known concerning the major Notch downstream targets, especially the onset and sequence in which they are modulated during normal development. As timing of regulation may be linked to many biological processes, we investigated and established a model of temporal patterning of major Notch downstream targets including broad, cut, and hindsight during Drosophila melanogaster egg chamber development. We confirmed the sequential order of Broad upregulation, Hindsight upregulation, and Cut downregulation. In addition, we showed that Notch signaling could be activated at stage 4, one stage earlier than the stage 5, a previously long-held belief. However, our further mitotic marker analysis re-stated that mitotic cycle continues until stage 5. Through our study, we once again validated the effectiveness and reliability of our MATLAB toolbox designed to systematically identify egg chamber stages based on area size, ratio, and additional morphological characteristics.
生物有机体需要复杂的信号交互作用,并对这些交互作用进行适当的调节,以影响生物过程。在这些复杂的网络中,最显著的一个是 Notch 途径。该途径的失调通常会导致生物体发育过程中的缺陷,并且可能是癌症发生和进展的原因。尽管之前的研究强调了这种信号通路及其所涉及的生物体过程的重要性,但对于 Notch 的主要下游靶标,尤其是它们在正常发育过程中被调节的起始和顺序,知之甚少。由于调节的时间可能与许多生物过程有关,我们研究并建立了一个模型,用于研究果蝇卵室发育过程中 Notch 的主要下游靶标(包括 Broad、Cut 和 Hindsight)的时间模式。我们证实了 Broad 的上调、Hindsight 的上调和 Cut 的下调的顺序。此外,我们还表明 Notch 信号可以在阶段 4 激活,比以前认为的阶段 5 早一个阶段。然而,我们进一步的有丝分裂标记分析再次表明,有丝分裂周期一直持续到阶段 5。通过我们的研究,我们再次验证了我们基于面积大小、比例和其他形态特征来系统地识别卵室阶段的 MATLAB 工具箱的有效性和可靠性。