侧板外胚层形成
中文名称
通路描述
在原始突起的后部到前部，具有不同发育命运的中胚层亚群被产生（参见 Arnold and Robertson 2009, Ferretti and Hadjantonakis 2019, Prummel et al. 2020, Zhai et al. 2021）。在小鼠中，这些亚群（从后到前）分别是：额外胚外中胚层；将形成心脏、四肢和血液的侧板中胚层；将形成节段的前突肌中胚层；将形成脊索的轴中胚层；最后，是终末内胚层。在人类和其他灵长类动物中，额外胚外中胚层似乎是在囊胚形成之前从内胚层中产生的，因此侧板中胚层是原始突起的第一个中胚层类型。在侧板中胚层中，由相邻的原始内胚层产生的 Hedgehog 信号启动了一个自我强化的转录回路（根据 Astorga and Carlsson 2007, Becker et al. 1997 中的小鼠同源物推断）。Hedgehog 蛋白 SHH 和 IHH 激活 FOXF1 的表达，这是侧板中胚层的标志物，在其诱导后（根据 Rojas et al. 2005, Astorga and Carlsson 2007 中的小鼠同源物推断）。BMP4 也可能在原始突起和侧板中胚层中激活 FOXH1（根据 Tseng et al. 2004 中的 Xenopus 同源物推断）。FOXF1 激活 BMP4 和 BMP4 与 FOXF1 共同激活 GATA4（根据 Rojas et al. 2005 中的小鼠同源物推断）。BMP4 维持 FOXF1 的表达。GATA4 维持其自身表达和 BMP4 的表达。FOXF1 和 GATA4 然后激活下游基因的表达，进一步分化侧板中胚层。在斑马鱼中，Eomesodermin、FoxH1 和 Mixl1 的联合活动，以及 Smad 蛋白诱导侧板中胚层，该机制可能在所有脊索动物中共享（Prummel et al. 2019）。
英文描述
RHO GTPases activate IQGAPs IQGAPs constitute a family of scaffolding proteins characterized by a calponin homology (CH) domain, a polyproline binding region (WW domain), a tandem of four IQ (isoleucine and glutamine-rich) repeats and a RAS GTPase-activating protein-related domain (GRD). Three IQGAPs have been identified in human, IQGAP1, IQGAP2 and IQGAP3. The best characterized is IQGAP1 and over 90 proteins have been reported to bind to it. IQGAPs integrate multiple signaling pathways and coordinate a large variety of cellular activities (White et al. 2012). IQGAP proteins IQGAP1, IQGAP2 and IQGAP3, bind activated RHO GTPases RAC1 and CDC42 via their GRD and stabilize them in their GTP-bound state (Kuroda et al. 1996, Swart-Mataraza et al. 2002, Wang et al. 2007). IQGAPs bind F-actin filaments via the CH domain and modulate cell shape and motility through regulation of G-actin/F-actin equilibrium (Brill et al. 1996, Fukata et al. 1997, Bashour et al. 1997, Wang et al. 2007, Pelikan-Conchaudron et al. 2011). Binding of IQGAPs to F-actin is inhibited by calmodulin binding to the IQ repeats (Bashour et al. 1997, Pelikan-Conchaudron et al. 2011). Based on IQGAP1 studies, IQGAPs presumably function as homodimers (Bashour et al. 1997).IQGAP1 is involved in the regulation of adherens junctions through its interaction with E-cadherin (CDH1) and catenins (CTTNB1 and CTTNA1) (Kuroda et al. 1998, Hage et al. 2009). IQGAP1 contributes to cell polarity and lamellipodia formation through its interaction with microtubules (Fukata et al. 2002, Suzuki and Takahashi 2008).
所含基因
31 个基因