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祖细胞对立极化 WNT 激活剂和抑制剂以协调组织发育。

Progenitors oppositely polarize WNT activators and inhibitors to orchestrate tissue development.

机构信息

Robin Chemers Neustein Laboratory of Mammalian Cell Biology and Development, Howard Hughes Medical Institute, The Rockefeller University, New York, United States.

The Francis Crick Institute, Midland Road, London, United Kingdom.

出版信息

Elife. 2020 Apr 20;9:e54304. doi: 10.7554/eLife.54304.

Abstract

To spatially co-exist and differentially specify fates within developing tissues, morphogenetic cues must be correctly positioned and interpreted. Here, we investigate mouse hair follicle development to understand how morphogens operate within closely spaced, fate-diverging progenitors. Coupling transcriptomics with genetics, we show that emerging hair progenitors produce both WNTs and WNT inhibitors. Surprisingly, however, instead of generating a negative feedback loop, the signals oppositely polarize, establishing sharp boundaries and consequently a short-range morphogen gradient that we show is essential for three-dimensional pattern formation. By establishing a morphogen gradient at the cellular level, signals become constrained. The progenitor preserves its WNT signaling identity and maintains WNT signaling with underlying mesenchymal neighbors, while its overlying epithelial cells become WNT-restricted. The outcome guarantees emergence of adjacent distinct cell types to pattern the tissue.

摘要

为了在发育组织中空间共存并区分命运,形态发生线索必须正确定位和解释。在这里,我们研究了小鼠毛囊的发育,以了解形态发生素如何在紧密间隔、命运分歧的祖细胞中发挥作用。我们将转录组学与遗传学相结合,表明新兴的毛发祖细胞既能产生 WNT,也能产生 WNT 抑制剂。然而,令人惊讶的是,这些信号并没有产生负反馈环,而是相反地极化,建立了鲜明的边界,从而形成了一个我们认为对三维模式形成至关重要的短程形态发生梯度。通过在细胞水平上建立形态发生梯度,信号受到限制。祖细胞保留其 WNT 信号身份,并与下面的间充质邻居保持 WNT 信号,而其上面的上皮细胞则成为 WNT 受限的。这一结果保证了相邻不同细胞类型的出现,以对组织进行模式化。

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