Vascularization is an essential event for both embryonic organ development and tissue repair in adults. During mouse tooth development, endothelial cells migrate into dental papilla during the cap stage, and form blood vessels through angiogenesis. Megakaryocytes and/or platelets, as other hematopoietic cells, express angiogenic molecules and can promote angiogenesis in adult tissues. However, it remains unknown which cells are responsible for attracting and leading blood vessels through the dental papilla during tooth development. Here we analyzed the spatiotemporal expression of c-Mpl mRNA in developing molar teeth of fetal mice. Expression patterns were then compared with those of several markers of hematopoietic cells as well as of angiogenic elements including CD41, erythropoietin receptor, CD34, angiopoietin-1 (Ang-1), Tie-2, and vascular endothelial growth factor receptor2 (VEGFR2) through hybridization or immunohistochemistry. Cells expressing c-Mpl mRNA was found in several parts of the developing tooth germ, including the peridental mesenchyme, dental papilla, enamel organ, and dental lamina. This expression occurred in a spatiotemporally controlled fashion. CD41-expressing cells were not detected during tooth development. The spatiotemporal expression pattern of c-Mpl mRNA in the dental papilla was similar to that of Ang-1, which preceded invasion of endothelial cells. Eventually, at the early bell stage, the c-Mpl mRNA signal was detected in morphologically differentiating odontoblasts that accumulated in the periphery of the dental papilla along the inner enamel epithelium layer of the future cusp region. During tooth development, several kinds of cells express c-Mpl mRNA in a spatiotemporally controlled fashion, including differentiating odontoblasts. We hypothesize that c-Mpl-expressing cells appearing in the forming dental papilla at the cap stage are odontoblast progenitor cells that migrate to the site of odontoblast differentiation. There they attract vascular endothelial cells into the forming dental papilla and lead cells toward the inner enamel epithelium layer through production of angiogenic molecules (e.g., Ang-1) during migration to the site of differentiation. C-Mpl may regulate apoptosis and/or proliferation of expressing cells in order to execute normal development of the tooth.

中文翻译：

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牙胚中c-Mpl mRNA的时空表达谱：血管化相关基因的比较表达动态

血管化是成人胚胎器官发育和组织修复的重要事件。在小鼠牙齿发育过程中，内皮细胞在帽期迁移到牙乳头，并通过血管生成形成血管。巨核细胞和/或血小板与其他造血细胞一样，表达血管生成分子并且可以促进成体组织中的血管生成。然而，目前尚不清楚在牙齿发育过程中哪些细胞负责吸引和引导血管通过牙乳头。在这里，我们分析了胎儿小鼠磨牙发育中 c-Mpl mRNA 的时空表达。然后将表达模式与造血细胞以及血管生成元件的几种标志物进行比较，包括 CD41、促红细胞生成素受体、CD34、血管生成素-1 (Ang-1)、Tie-2 和血管内皮生长因子受体 2 (VEGFR2)杂交或免疫组织化学。在发育中的牙胚的几个部分中发现了表达c-Mpl mRNA的细胞，包括牙周间充质、牙乳头、牙釉质器官和牙板。这种表达以时空控制的方式发生。在牙齿发育过程中未检测到表达 CD41 的细胞。牙乳头中c-Mpl mRNA的时空表达模式与Ang-1的时空表达模式相似，后者先于内皮细胞的侵袭。最终，在钟早期，在形态分化的成牙本质细胞中检测到了 c-Mpl mRNA 信号，这些成牙本质细胞沿着未来牙尖区域的内釉质上皮层积聚在牙乳头周围。在牙齿发育过程中，多种细胞以时空控制的方式表达 c-Mpl mRNA，包括分化的成牙本质细胞。我们假设在帽期形成牙乳头中出现的表达 c-Mpl 的细胞是迁移到成牙本质细胞分化部位的成牙本质细胞祖细胞。在那里，它们将血管内皮细胞吸引到正在形成的牙乳头中，并在迁移到分化部位的过程中通过产生血管生成分子（例如Ang-1）引导细胞向内釉质上皮层移动。 C-Mpl可以调节表达细胞的凋亡和/或增殖以执行牙齿的正常发育。