Trophectoderm formation: regulation of morphogenesis and gene expressions by RHO, ROCK, cell polarity, and HIPPO signaling.
Trophectoderm formation: regulation of morphogenesis and gene expressions by RHO, ROCK, cell polarity, and HIPPO signaling.
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DOI：
10.1530/rep-21-0478
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发表时间：
2022-10-01
期刊：
影响因子：
3.8
通讯作者：
Marikawa, Yusuke
中科院分区：
文献类型：
--
作者：
Alarcon, Vernadeth B.;Marikawa, Yusuke
滋养外胚层是胎盘哺乳动物着床前发育过程中最先分化的组织。它构成胚泡的外上皮层，负责孵化、子宫附着和胎盘形成。因此，它的形成是使哺乳动物能够胎生的关键的初始步骤。在这里，我们首先从形态和分子水平描述TE形成的一般特征。未来的TE细胞通过建立顶端-基底细胞极性、细胞间连接、微腔和渗透梯度，形成包裹扩张的液体充盈腔的上皮层。一组独特的基因在TE中表达，这些基因编码着床后胎盘滋养层细胞发育所必需的转录因子。TE特异性基因的表达是由河马信号的抑制所驱动的，而河马信号的抑制依赖于预先建立的顶端-基底极性。然后，我们讨论了RAS同源家族成员(RHO)和RHO相关的含有蛋白激酶的螺旋卷曲(ROCK)作为TE形成的重要调节因子所起的特殊作用。Rho和ROCK调节肌动球蛋白的细胞骨架、尖-基极性、细胞间连接和河马信号，从而协调TE的上皮化和基因表达。对TE形成的分子机制的了解对于人类和农场动物的辅助生殖技术至关重要，因为它为帮助改进胚胎处理和选择程序以实现更好的生殖结果提供了基础。滋养外胚层是哺乳动物早期胚胎中第一个分化的组织，是孵化、着床和胎盘形成所必需的。本文就Rho和ROCK在滋养外胚层形成的分子和细胞调控中的作用作一综述。
The trophectoderm (TE) is the first tissue to differentiate during the preimplantation development of placental mammals. It constitutes the outer epithelial layer of the blastocyst, and is responsible for hatching, uterine attachment, and placentation. Thus, its formation is the key initial step that enables the viviparity of mammals. Here, we first describe the general features of TE formation at the morphological and molecular levels. Prospective TE cells form an epithelial layer enclosing an expanding fluid-filled cavity by establishing the apical-basal cell polarity, intercellular junctions, microlumen, and osmotic gradient. A unique set of genes is expressed in TE that encode the transcription factors essential for the development of trophoblasts of the placenta upon implantation. TE-specific gene expressions are driven by the inhibition of HIPPO signaling, which is dependent on the prior establishment of the apical-basal polarity. We then discuss the specific roles of Ras homolog family members (RHO) and RHO-associated coiled-coil containing protein kinases (ROCK) as essential regulators of TE formation. RHO and ROCK modulate the actomyosin cytoskeleton, apical-basal polarity, intercellular junctions, and HIPPO signaling, thereby orchestrating the epithelialization and gene expressions in TE. Knowledge of the molecular mechanisms underlying TE formation is crucial for assisted reproductive technologies in human and farm animals, as it provides foundation to help improve procedures for embryo handling and selection to achieve better reproductive outcomes. Trophectoderm is the first tissue to differentiate in the early mammalian embryo, and is essential for hatching, implantation, and placentation. This review article discusses the roles of RHO and ROCK in the molecular and cellular regulation of trophectoderm formation.