Department of Developmental and Stem Cell Biology, Institut Pasteur, F-75015, Paris, France.
CNRS, UMR3738, F-75015, Paris, France.
Nat Commun. 2017 Nov 17;8(1):1594. doi: 10.1038/s41467-017-01482-8.
Embryo-scale morphogenesis arises from patterned mechanical forces. During Drosophila gastrulation, actomyosin contractility drives apical constriction in ventral cells, leading to furrow formation and mesoderm invagination. It remains unclear whether and how mechanical properties of the ectoderm influence this process. Here, we show that Neuralized (Neur), an E3 ubiquitin ligase active in the mesoderm, regulates collective apical constriction and furrow formation. Conversely, the Bearded (Brd) proteins antagonize maternal Neur and lower medial-apical contractility in the ectoderm: in Brd-mutant embryos, the ventral furrow invaginates properly but rapidly unfolds as medial MyoII levels increase in the ectoderm. Increasing contractility in the ectoderm via activated Rho similarly triggers furrow unfolding whereas decreasing contractility restores furrow invagination in Brd-mutant embryos. Thus, the inhibition of Neur by Brd in the ectoderm differentiates the mechanics of the ectoderm from that of the mesoderm and patterns the activity of MyoII along the dorsal-ventral axis.
胚胎尺度形态发生源于模式化的机械力。在果蝇原肠胚形成过程中,肌动球蛋白收缩力驱动腹侧细胞的顶端收缩,导致沟的形成和中胚层的内陷。目前尚不清楚上皮细胞的机械特性是否以及如何影响这一过程。在这里,我们发现神经调节蛋白(Neur),一种在中胚层中活跃的 E3 泛素连接酶,调节集体顶端收缩和沟的形成。相反,胡茬(Brd)蛋白拮抗母体 Neur,并降低上皮细胞中的中-顶向收缩性:在 Brd 突变体胚胎中,腹侧沟正确地内陷,但随着上皮细胞中 MyoII 水平的增加,迅速展开。通过激活 Rho 增加上皮细胞的收缩性同样会引发沟的展开,而降低收缩性则会恢复 Brd 突变体胚胎中的沟内陷。因此,Brd 在上皮细胞中对 Neur 的抑制将上皮细胞的力学特性与中胚层的力学特性区分开来,并沿着背腹轴对 MyoII 的活性进行模式化。