胚层祖细胞的协调运动在背侧达到高峰,其中Bmp信号梯度较低,腹侧最小,其中Bmp梯度较高。这种动态的细胞运动受到各种信号通路的相互作用的调节。非规范的Wnt信号级联作为会聚和延伸细胞运动的关键调节器,通过激活小的GTPases,如Rho,Rab,还有Rac.然而,腹侧细胞运动受限的根本原因仍然难以捉摸。探讨一个关键调节因子在腹侧限制原肠胚细胞运动中的作用,我们研究了Bmp4-direct靶基因,嘶嘶声,评估其在抑制非规范Wnt信号传导中的潜在作用。在我们目前的研究中,我们证明了sizzled的异位表达以剂量依赖性方式导致胃泌素缺陷,不改变细胞命运规范。sizzled的过表达导致激活素处理的动物帽和凯勒外植体的伸长降低。此外,我们的免疫沉淀测定法揭示了Sizzled与非经典Wnt配体蛋白(Wnt5和Wnt11)的物理相互作用。此外,过表达后,参与Wnt信号介导的小GTP酶(RhoA和Rac1)的激活减弱。总之,我们的发现表明,Bmp4信号传导通过诱导非洲爪狼早期原肠胚形成过程中的sizzle表达来负向调节胚胎腹侧的细胞运动。
The coordinated movement of germ layer progenitor cells reaches its peak at the dorsal side, where the Bmp signaling gradient is low, and minimum at the ventral side, where the Bmp gradient is high. This dynamic cell movement is regulated by the interplay of various signaling pathways. The noncanonical Wnt signaling cascade serves as a pivotal regulator of convergence and extension cell movement, facilitated by the activation of small GTPases such as Rho, Rab, and Rac. However, the underlying cause of limited cell movement at the ventral side remains elusive. To explore the functional role of a key regulator in constraining gastrulation cell movement at the ventral side, we investigated the Bmp4-direct target gene, sizzled (szl), to assess its potential role in inhibiting noncanonical Wnt signaling. In our current study, we demonstrated that ectopic expression of szl led to gastrulation defects in a dose-dependent manner without altering cell fate specification. Overexpression of szl resulted in decreased elongation of Activin-treated animal cap and Keller explants. Furthermore, our immunoprecipitation assay unveiled the physical interaction of Szl with noncanonical Wnt ligand proteins (Wnt5 and Wnt11). Additionally, the activation of small GTPases involved in Wnt signaling mediation (RhoA and Rac1) was diminished upon szl overexpression. In summary, our findings suggest that Bmp4 signaling negatively modulates cell movement from the ventral side of the embryo by inducing szl expression during early Xenopus gastrulation.