Kameda Yoko, Ito Masataka, Nishimaki Toshiyuki, Gotoh Noriko
Department of Anatomy, Kitasato University School of Medicine, Sagamihara, Kanagawa 228-8555, Japan.
Dev Biol. 2008 Feb 1;314(1):236-47. doi: 10.1016/j.ydbio.2007.12.002. Epub 2007 Dec 8.
The docking protein FRS2 alpha is an important mediator of fibroblast growth factor (FGF)-induced signal transduction, and functions by linking FGF receptors (FGFRs) to a variety of intracellular signaling pathways. We show that the carotid body is absent in FRS2 alpha(2F/2F) mice, in which the Shp2-binding sites of FRS2 alpha are disrupted. We also show that the carotid body rudiment is not formed in the wall of the third arch artery in mutant embryos. In wild-type mice, the superior cervical ganglion of the sympathetic trunk connects to the carotid body in the carotid bifurcation region, and extends thick nerve bundles into the carotid body. In FRS2 alpha(2F/2F) mice, the superior cervical ganglion was present in the lower cervical region as an elongated feature, but failed to undergo cranio-ventral migration. In addition, few neuronal processes extended from the ganglion into the carotid bifurcation region. The number of carotid sinus nerve fibers that reached the carotid bifurcation region was markedly decreased, and baroreceptor fibers belonging to the glossopharyngeal nerve were absent from the basal part of the internal carotid artery in FRS2 alpha(2F/2F) mutant mice. In some of the mutant mice (5 out of 14), baroreceptors and some glomus cells were distributed in the wall of the common carotid artery, onto which the sympathetic ganglion abutted. We propose that the sympathetic ganglion provides glomus cell precursors into the third arch artery derivative in the presence of sensory fibers of the glossopharyngeal nerve.
对接蛋白FRS2α是成纤维细胞生长因子（FGF）诱导的信号转导的重要介质，其功能是将FGF受体（FGFRs）与多种细胞内信号通路相连接。我们发现，FRS2α（2F/2F）小鼠中没有颈动脉体，在这些小鼠中FRS2α的Shp2结合位点被破坏。我们还发现，突变胚胎的第三主动脉弓壁中未形成颈动脉体原基。在野生型小鼠中，交感干的颈上神经节在颈动脉分叉区域与颈动脉体相连，并向颈动脉体延伸粗大的神经束。在FRS2α（2F/2F）小鼠中，颈上神经节在颈下部区域呈细长状存在，但未能进行颅腹侧迁移。此外，从神经节延伸到颈动脉分叉区域的神经突很少。到达颈动脉分叉区域的颈动脉窦神经纤维数量明显减少，并且在FRS2α（2F/2F）突变小鼠的颈内动脉基部没有属于舌咽神经的压力感受器纤维。在一些突变小鼠（14只中有5只）中，压力感受器和一些球细胞分布在颈总动脉壁上，交感神经节与之相邻。我们提出，在存在舌咽神经感觉纤维的情况下，交感神经节为第三主动脉弓衍生物提供球细胞前体。
