Department of Orthopaedic Surgery, San Francisco General Hospital, The University of California San Francisco, School of Medicine, San Francisco, California 94110, USA.
Dev Dyn. 2012 Apr;241(4):732-40. doi: 10.1002/dvdy.23764.
Multiple fibroblast growth factor (Fgf) ligands are expressed in the forebrain and facial ectoderm, and vascular endothelial growth factor (VEGF) is expressed in the facial ectoderm. Both pathways activate the MAP kinase cascade and can be suppressed by SU5402. We placed a bead soaked in SU5402 into the brain after emigration of neural crest cells was complete.
Within 24 hr we observed reduced pMEK and pERK staining that persisted for at least 48 hr. This was accompanied by significant apoptosis in the face. By day 15, the upper beaks were truncated. Molecular changes in the FNP were also apparent. Normally, Shh is expressed in the frontonasal ectodermal zone and controls patterned growth of the upper jaw. In treated embryos, Shh expression was reduced. Both the structural and molecular deficits were mitigated after transplantation of FNP-derived mesenchymal cells.
Thus, mesenchymal cells actively participate in signaling interactions of the face, and the absence of neural crest cells in neurocristopathies may not be merely structural.
多种成纤维细胞生长因子（Fgf）配体在前脑和面部外胚层中表达，血管内皮生长因子（VEGF）在面部外胚层中表达。这两种途径都能激活 MAP 激酶级联反应，且能被 SU5402 抑制。我们在神经嵴细胞迁移完成后，将浸有 SU5402 的珠状物置于脑内。
在 24 小时内，我们观察到 pMEK 和 pERK 染色减少，这种现象至少持续了 48 小时。这伴随着面部的显著凋亡。到第 15 天，上颌骨被截断。FNP 中的分子变化也很明显。正常情况下，Shh 在额鼻外胚层区表达，并控制上颌骨的图案生长。在处理过的胚胎中，Shh 的表达减少。FNP 衍生的间充质细胞移植后，结构和分子缺陷都得到了缓解。
因此，间充质细胞积极参与面部的信号转导相互作用，神经嵴细胞缺失在神经嵴病变中可能不仅仅是结构上的。
