中间胚层的形成
中文名称
通路描述
中间胚层产生泌尿生殖系统，包括性腺和肾脏的所有组成部分。前部中间胚层产生尿生殖上皮，后部中间胚层产生肾中胚层。中间胚层的诱导是由侧板胚层（高 BMP 活性）和旁侧板胚层（低 BMP 活性）之间的分级 BMP 信号水平引起的（小鼠胚胎数据：James and Schultheiss 2005，综述 Davidson et al. 2019）。中间胚层在前后轴上的指定受 Wnt 和 FGF 信号以及视黄酸信号的影响，存在背腹和头尾梯度（小鼠胚胎数据：Cartry et al. 2006，综述 Davidson et al. 2019）。在小鼠中，中间胚层的第一个观察到的标记物是 Osr1 和 Lhx1，它们也在侧板胚层中表达。随后，Pax2 和 Pax8 在中间胚层中特异性表达。在小鼠胚胎中，敲除实验表明 Osr1 激活 Lhx1 和 Pax2（Wang et al. 2005），Lhx1 激活 Pax2（Tsang et al. 2000），Pax2 激活 Lhx1 和 Osr1（Boualia et al. 2013，Ranghini and Dressler 2015，综述 Marcotte et al. 2013）。Foxc1 和 Foxc2 在旁侧板胚层中产生，抑制 Lhx1 和 Osr1，从而限制中间胚层的扩展（Wilm et al. 2004）。在体外，人多能干细胞可通过 Wnt 激动剂（CHIR99021）处理形成中间胚层，随后用 FGF2 和视黄酸处理（Lam et al. 2014）。
英文描述
Epithelial-Mesenchymal Transition (EMT) during gastrulation During the epithelial-mesenchymal transition (EMT) during gastrulation, epithelial cells in the primitive streak transition to dissociated mesenchymal cells, allowing them to leave the epithelial epiblast (reviewed in Francou and Anderson 2020). EMT is induced by FGF, WNT, NODAL, and BMP signaling pathways that are present on the posterior side of the embryo (reviewed in Morgani and Hadjantonakis 2021). The FGF pathway in particular has been implicated in the regulation of EMT during gastrulation (inferred from mouse embryos in Ciruna and Rossant 2001). In later stage cancer cells the TGFbeta signaling pathway is a major inducer of EMT that leads to metastasis (reviewed in Hao et al. 2019). During gastrulation BMP4 and NODAL of the TGFbeta pathways are also probably involved in EMT (Martyn et al. 2018).
This epithelial-mesenchymal transition (EMT) is responsible for formation of mesoderm. An incomplete EMT appears to be responsible for formation of endoderm (inferred from mouse embryos in Viotti et al. 2014, Scheibner et al. 2021). Prospective definitive endoderm cells leave the epiblast layer together with mesoderm cells and eventually integrate and displace the extraembryonic visceral endoderm layer (inferred from mouse embryos in Viotti et al. 2014).
SNAIL (SNAI1), a transcription factor activated in the primitive streak (inferred from the mouse homolog in Carver et al. 2001), participates in crucial events in the EMT that creates mesoderm: the downregulation of cell adhesion proteins E-cadherin (Cadherin-1, CDH1), Occludin (OLCN), and Claudins that results in loss of contact between cells. Instead, cells switch to expression of N-cadherin and mesenchymal gene programs.
Both EOMES and TBXT activate expression of SNAI1 at the primitive streak but not in definitive endoderm progenitors. SNAI1 represses CDH1 expression (reviewed in Bardot et al. 2020), OCLN expression (inferred from mouse homologs in Ikenouchi et al. 2003), and expression of Claudins (inferred from mouse homologs in Ikenouchi et al. 2003). Downregulation of CDH1 also occurs posttranslationally through an incompletely characterized mechanism involving NIK, p38 MAPK, and EBP41L5 (inferred from mouse homologs in Lee et al. 2007, Hirano et al. 2008). SNAI1 but not SNAI2 is required for proper EMT during gastrulation. Other factors required for EMT during gastrulation include p120-catenin, which regulates WNT signaling and EMT (inferred from mouse homologs in Hernandez-Martinez et al. 2019); Crumbs2, which promotes cell ingression (inferred from mouse homologs in Ramkumar et al. 2016); RhoA and microtubules, which control cell basement interactions (inferred from mouse homologs in Nakaya et al. 2008); and p38 and p38 interacting protein, which are critical for downregulating E-Cadherin (Zohn et al. 2006).
This epithelial-mesenchymal transition (EMT) is responsible for formation of mesoderm. An incomplete EMT appears to be responsible for formation of endoderm (inferred from mouse embryos in Viotti et al. 2014, Scheibner et al. 2021). Prospective definitive endoderm cells leave the epiblast layer together with mesoderm cells and eventually integrate and displace the extraembryonic visceral endoderm layer (inferred from mouse embryos in Viotti et al. 2014).
SNAIL (SNAI1), a transcription factor activated in the primitive streak (inferred from the mouse homolog in Carver et al. 2001), participates in crucial events in the EMT that creates mesoderm: the downregulation of cell adhesion proteins E-cadherin (Cadherin-1, CDH1), Occludin (OLCN), and Claudins that results in loss of contact between cells. Instead, cells switch to expression of N-cadherin and mesenchymal gene programs.
Both EOMES and TBXT activate expression of SNAI1 at the primitive streak but not in definitive endoderm progenitors. SNAI1 represses CDH1 expression (reviewed in Bardot et al. 2020), OCLN expression (inferred from mouse homologs in Ikenouchi et al. 2003), and expression of Claudins (inferred from mouse homologs in Ikenouchi et al. 2003). Downregulation of CDH1 also occurs posttranslationally through an incompletely characterized mechanism involving NIK, p38 MAPK, and EBP41L5 (inferred from mouse homologs in Lee et al. 2007, Hirano et al. 2008). SNAI1 but not SNAI2 is required for proper EMT during gastrulation. Other factors required for EMT during gastrulation include p120-catenin, which regulates WNT signaling and EMT (inferred from mouse homologs in Hernandez-Martinez et al. 2019); Crumbs2, which promotes cell ingression (inferred from mouse homologs in Ramkumar et al. 2016); RhoA and microtubules, which control cell basement interactions (inferred from mouse homologs in Nakaya et al. 2008); and p38 and p38 interacting protein, which are critical for downregulating E-Cadherin (Zohn et al. 2006).
所含基因
4 个基因