aPKC regulates apical constriction to prevent tissue rupture in the Drosophila follicular epithelium.
aPKC regulates apical constriction to prevent tissue rupture in the Drosophila follicular epithelium.
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DOI：
10.1016/j.cub.2022.08.063
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发表时间：
2022-10-24
期刊：
影响因子：
9.2
通讯作者：
Morais-de-Sa, Eurico
中科院分区：
文献类型：
--
作者：
Osswald, Mariana;Barros-Carvalho, Andre;Carmo, Ana M.;Loyer, Nicolas;Gracio, Patricia C.;Sunkel, Claudio E.;Homem, Catarina C. F.;Januschke, Jens;Morais-de-Sa, Eurico
顶端-基底极性是一种重要的上皮特征，由进化上保守的 PAR-aPKC 极性网络控制。极性蛋白的失调会在发育和疾病过程中破坏组织组织，但由于极性丧失的广泛影响，其潜在机制尚不清楚。在这里，我们通过直接观察活体成年果蝇和离体培养的卵巢快速光遗传学失活后的组织解体，揭示了果蝇 aPKC 如何维持上皮结构。我们发现，增殖性滤泡上皮中的快速 aPKC 扰动会产生较大的上皮间隙，这是由于顶端收缩增加，而不是顶端-基底极性丧失所致。因此，我们可以通过增加和减少肌动球蛋白驱动的收缩力来调节上皮间隙的发生率。我们追踪这些大上皮间隙的起源是分裂细胞旁边的组织破裂。实时成像显示，aPKC 扰动会在几分钟内诱导非有丝分裂细胞的顶端收缩，产生最终使分裂细胞和邻近细胞分离的拉力。我们进一步证明，上皮破裂需要顶端收缩的整体增加，因为非收缩细胞的存在可以防止上皮破裂。相反，通过光诱导将 RhoGEF2 募集到根尖侧来整体诱导根尖张力足以产生组织破裂。因此，我们的工作揭示了 aPKC 在极性和肌动球蛋白调节中的作用是可分离的，并提供了第一个体内证据，证明过度的组织应激可以在增殖过程中破坏上皮屏障。光遗传学聚类通过高时间控制在体内和体外破坏 aPKC aPKC 下调多个果蝇组织中的顶端收缩力 aPKC 快速失活导致分裂滤泡细胞旁边的组织破裂 顶端收缩的增加可以在增殖过程中破坏上皮屏障 Osswald 等人。利用光遗传学和化学遗传学快速调节果蝇组织中的 aPKC 活性，并将其作为顶端肌动球蛋白网络抑制剂的作用与其在细胞极性中的功能分开。他们表明，急性诱导顶端收缩会迅速导致果蝇卵巢中分裂细胞旁边的上皮组织破裂。
Apical-basal polarity is an essential epithelial trait controlled by the evolutionarily conserved PAR-aPKC polarity network. Dysregulation of polarity proteins disrupts tissue organization during development and in disease, but the underlying mechanisms are unclear due to the broad implications of polarity loss. Here, we uncover how Drosophila aPKC maintains epithelial architecture by directly observing tissue disorganization after fast optogenetic inactivation in living adult flies and ovaries cultured ex vivo. We show that fast aPKC perturbation in the proliferative follicular epithelium produces large epithelial gaps that result from increased apical constriction, rather than loss of apical-basal polarity. Accordingly, we can modulate the incidence of epithelial gaps by increasing and decreasing actomyosin-driven contractility. We traced the origin of these large epithelial gaps to tissue rupture next to dividing cells. Live imaging shows that aPKC perturbation induces apical constriction in non-mitotic cells within minutes, producing pulling forces that ultimately detach dividing and neighboring cells. We further demonstrate that epithelial rupture requires a global increase of apical constriction, as it is prevented by the presence of non-constricting cells. Conversely, a global induction of apical tension through light-induced recruitment of RhoGEF2 to the apical side is sufficient to produce tissue rupture. Hence, our work reveals that the roles of aPKC in polarity and actomyosin regulation are separable and provides the first in vivo evidence that excessive tissue stress can break the epithelial barrier during proliferation. Optogenetic clustering disrupts aPKC in vivo and ex vivo with high temporal control aPKC downregulates apical contractility in multiple Drosophila tissues Rapid aPKC inactivation causes tissue rupture next to dividing follicle cells Increased apical constriction can break the epithelial barrier during proliferation Osswald et al. use optogenetics and chemical genetics to rapidly modulate aPKC activity in Drosophila tissues and untangle its role as an inhibitor of apical actomyosin networks from its function in cell polarity. They show that acute induction of apical constriction rapidly leads to epithelial tissue rupture next to dividing cells in the fly ovary.
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