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在果蝇翅膀形态发生过程中,Fat-Dachsous平面极性通路与铰链收缩相互竞争,以确定极化细胞行为的方向。

The Fat-Dachsous planar polarity pathway competes with hinge contraction to orient polarized cell behaviors during Drosophila wing morphogenesis.

作者信息

Trinidad Larra, Fletcher Alexander G, Strutt David

机构信息

School of Biosciences, University of Sheffield, Firth Court, Sheffield, S10 2TN, UK.

School of School of Mathematical and Physical Sciences, University of Sheffield, Hicks Building, Sheffield S3 7RH, UK.

出版信息

Curr Biol. 2025 Jan 20;35(2):422-430.e3. doi: 10.1016/j.cub.2024.11.058. Epub 2024 Dec 20.

Abstract

During tissue morphogenesis, an interplay of biochemical pathways and mechanical cues regulates polarized cell behaviors, the balance of which leads to tissues reaching their correct shape and size. A well-studied example of a biochemical regulator is the highly conserved Fat-Dachsous (Ft-Ds) pathway that coordinates planar polarized cell behaviors and growth in epithelial tissues. For instance, in the Drosophila larval wing disc, the Ft-Ds pathway acts via the atypical myosin Dachs to control tissue shape by promoting the orientation of cell divisions primarily in a proximodistal (PD) direction. Here, we investigate interactions between Ft-Ds planar polarity and mechanical forces in the developing Drosophila pupal wing. We show that in the early stages of pupal wing development (16-18 h after puparium formation), anteroposterior (AP)-oriented cell divisions and T1 transitions are controlled by the Ft-Ds pathway acting via Dachs. Shortly thereafter, PD-oriented tissue tension is induced across the wing blade by the process of hinge contraction. This opposes the control of Dachs over polarized cell behaviors in a tug-of-war fashion, resulting in more PD-oriented cell divisions and T1s. Furthermore, increased PD tissue tension stabilizes Ft along PD-oriented junctions, suggesting that biomechanical feedback on the Ft-Ds pathway resists the effects of hinge contraction on cell shape. We also show that loss of Dachs results in increased myosin-II stability at cell junctions, revealing compensatory interactions between these two myosins. Overall, we propose that Ft-Ds pathway function constitutes a mechanism whereby tissues are buffered against mechanical perturbations.

摘要

在组织形态发生过程中,生化途径与机械信号之间的相互作用调节着极化细胞行为,二者的平衡使组织达到正确的形状和大小。一个经过充分研究的生化调节因子的例子是高度保守的Fat-Dachsous(Ft-Ds)途径,它在上皮组织中协调平面极化细胞行为和生长。例如,在果蝇幼虫翅盘中,Ft-Ds途径通过非典型肌球蛋白Dachs起作用,主要通过促进细胞分裂主要沿近远轴(PD)方向的定向来控制组织形状。在这里,我们研究了果蝇蛹翅发育过程中Ft-Ds平面极性与机械力之间的相互作用。我们发现,在蛹翅发育的早期阶段(蛹形成后16 - 18小时),前后轴(AP)方向的细胞分裂和T1转变由通过Dachs起作用的Ft-Ds途径控制。此后不久,铰链收缩过程在整个翅片上诱导出沿PD方向的组织张力。这在一场拔河比赛中对抗了Dachs对极化细胞行为的控制,导致更多沿PD方向的细胞分裂和T1转变。此外,增加的PD组织张力使Ft沿着PD方向的连接处稳定,这表明对Ft-Ds途径的生物力学反馈抵抗了铰链收缩对细胞形状的影响。我们还表明,Dachs的缺失导致细胞连接处肌球蛋白-II稳定性增加,揭示了这两种肌球蛋白之间的补偿性相互作用。总体而言,我们提出Ft-Ds途径功能构成了一种机制,通过该机制组织可以缓冲机械扰动。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/13fc/7617321/7b28a45a3533/EMS202683-f005.jpg

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