Mouse embryo geometry drives formation of robust signaling gradients through receptor localization.
Mouse embryo geometry drives formation of robust signaling gradients through receptor localization.
复制标题
小鼠胚胎几何形状通过受体定位驱动强大的信号梯度的形成。
DOI：
10.1038/s41467-019-12533-7
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发表时间：
2019
影响因子：
16.6
通讯作者：
Ramanathan,Sharad
中科院分区：
文献类型：
--
作者：
Zhang,Zhechun;Zwick,Steven;Loew,Ethan;Grimley,JoshuaS;Ramanathan,Sharad
形态发生信号对于胚胎发生过程中的细胞命运规范至关重要。已知一些感知这些形态发生素的受体仅定位于体外极化细胞系的顶膜或基底外侧膜。这种定位如何影响发育胚胎中的形态素感知和模式仍然未知。在这里，我们表明，早期小鼠胚胎中强大的 BMP 信号梯度的形成取决于 BMP 受体的限制性基底外侧定位。受体错误定位于顶膜导致体内小鼠外胚层异位 BMP 信号传导。根据数学模型、体外人类胚胎干细胞和体内小鼠胚胎的证据，我们发现 BMP 受体和配体的几何区划创建了一个信号梯度，可以缓冲波动。我们的结果证明了受体定位和胚胎几何形状在胚胎发生过程中形成形态发生素信号传导的重要性。
Morphogen signals are essential for cell fate specification during embryogenesis. Some receptors that sense these morphogens are known to localize to only the apical or basolateral membrane of polarized cell lines in vitro. How such localization affects morphogen sensing and patterning in the developing embryo remains unknown. Here, we show that the formation of a robust BMP signaling gradient in the early mouse embryo depends on the restricted, basolateral localization of BMP receptors. The mis-localization of receptors to the apical membrane results in ectopic BMP signaling in the mouse epiblast in vivo. With evidence from mathematical modeling, human embryonic stem cells in vitro, and mouse embryos in vivo, we find that the geometric compartmentalization of BMP receptors and ligands creates a signaling gradient that is buffered against fluctuations. Our results demonstrate the importance of receptor localization and embryo geometry in shaping morphogen signaling during embryogenesis.