Growth factor-mediated mesodermal cell guidance and skeletogenesis during sea urchin gastrulation
Growth factor-mediated mesodermal cell guidance and skeletogenesis during sea urchin gastrulation
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DOI：
10.1242/dev.100479
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发表时间：
2013-10-15
期刊：
影响因子：
4.6
通讯作者：
Ettensohn, Charles A.
中科院分区：
文献类型：
--
作者：
Adomako-Ankomah, Ashrifia;Ettensohn, Charles A.
生长因子信号通路为许多后生动物原肠胚形成过程中的中胚层细胞提供了必要的线索。最近的研究表明，在海胆原肠胚形成过程中，VEGF和FGF通路为初级间充质细胞（PMC）提供了指导和分化线索，尽管这些通路的相对贡献及其调节的细胞行为尚未完全了解。在这里，我们表明，FGF和VEGF配体表达在不同的领域在胚胎外胚层的Lytechinus variegatus。我们发现PMC指导在Lv-vegf 3 morphants中被特异性破坏，这些胚胎无法形成骨骼元件。相比之下，PMC迁移是不受影响的Lv-fgfa吗啡样，和良好的模式，但缩短的骨骼元素的形式。我们使用一种VEGFR抑制剂阿西替尼，表明VEGF信号不仅对PMC迁移的初始阶段（亚赤道环形成）至关重要，而且对第二阶段（向动物极迁移）也至关重要。然而，VEGF信号传导对于PMC融合不是必需的。在PMC迁移完成后抑制VEGF信号传导导致骨骼发生的显著缺陷，选择性地阻断支持幼虫臂的骨骼杆的伸长，但不阻断在胚胎背侧区域形成的杆。Nanostring nCounter对PMC基因调控网络中的100个基因进行的分析显示，许多基因的表达减少，这些基因在vegf 3 morphants中的生物矿化中具有已证实或预测的作用。我们的研究导致更好地了解生长因子在海胆原肠胚形成和骨骼发育中所起的作用。
Growth factor signaling pathways provide essential cues to mesoderm cells during gastrulation in many metazoans. Recent studies have implicated the VEGF and FGF pathways in providing guidance and differentiation cues to primary mesenchyme cells (PMCs) during sea urchin gastrulation, although the relative contributions of these pathways and the cell behaviors they regulate are not fully understood. Here, we show that FGF and VEGF ligands are expressed in distinct domains in the embryonic ectoderm of Lytechinus variegatus. We find that PMC guidance is specifically disrupted in Lv-vegf3 morphants and these embryos fail to form skeletal elements. By contrast, PMC migration is unaffected in Lv-fgfa morphants, and well-patterned but shortened skeletal elements form. We use a VEGFR inhibitor, axitinib, to show that VEGF signaling is essential not only for the initial phase of PMC migration (subequatorial ring formation), but also for the second phase (migration towards the animal pole). VEGF signaling is not required, however, for PMC fusion. Inhibition of VEGF signaling after the completion of PMC migration causes significant defects in skeletogenesis, selectively blocking the elongation of skeletal rods that support the larval arms, but not rods that form in the dorsal region of the embryo. Nanostring nCounter analysis of similar to 100 genes in the PMC gene regulatory network shows a decrease in the expression of many genes with proven or predicted roles in biomineralization in vegf3 morphants. Our studies lead to a better understanding of the roles played by growth factors in sea urchin gastrulation and skeletogenesis.