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Mechanism and implications of morphogen shuttling: Lessons learned from dorsal and Cactus in Drosophila.
Developmental Biology ( IF 2.5 ) Pub Date : 2020-01-24 , DOI: 10.1016/j.ydbio.2020.01.011
Allison E Schloop 1 , Sophia Carrell-Noel 2 , Jeramey Friedman 2 , Alexander Thomas 2 , Gregory T Reeves 3
Affiliation  

In a developing animal, morphogen gradients act to pattern tissues into distinct domains of cell types. However, despite their prevalence in development, morphogen gradient formation is a matter of debate. In our recent publication, we showed that the Dorsal/NF-κB morphogen gradient, which patterns the DV axis of the early Drosophila embryo, is partially established by a mechanism of facilitated diffusion. This mechanism, also known as "shuttling," occurs when a binding partner of the morphogen facilitates the diffusion of the morphogen, allowing it to accumulate at a given site. In this case, the inhibitor Cactus/IκB facilitates the diffusion of Dorsal/NF-κB. In the fly embryo, we used computation and experiment to not only show that shuttling occurs in the embryo, but also that it enables the viability of embryos that inherit only one copy of dorsal maternally. In this commentary, we further discuss our evidence behind the shuttling mechanism, the previous literature data explained by the mechanism, and how it may also be critical for robustness of development. Finally, we briefly provide additional experimental data pointing toward an interaction between Dorsal and BMP signaling that is likely affected by shuttling.

中文翻译:


形态发生素穿梭的机制和意义:从果蝇背部和仙人掌中吸取的教训。



在发育中的动物中,形态发生素梯度将组织图案化为不同的细胞类型域。然而,尽管形态发生素梯度的形成在发育中很普遍,但它的形成仍然是一个有争议的问题。在我们最近的出版物中,我们表明,Dorsal/NF-κB 形态发生素梯度(其形成早期果蝇胚胎的 DV 轴)部分是通过促进扩散机制建立的。这种机制也称为“穿梭”,当形态发生素的结合伴侣促进形态发生素的扩散,使其在给定位点积聚时,就会发生这种机制。在这种情况下,抑制剂 Cactus/IκB 促进 Dorsal/NF-κB 的扩散。在果蝇胚胎中,我们使用计算和实验不仅表明穿梭发生在胚胎中,而且还表明它使仅继承一份母体背侧拷贝的胚胎具有活力。在这篇评论中,我们进一步讨论了穿梭机制背后的证据、该机制解释的先前文献数据,以及它如何对发展的稳健性至关重要。最后,我们简要提供了额外的实验数据,表明 Dorsal 和 BMP 信号之间的相互作用可能受到穿梭的影响。
更新日期:2020-04-20
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