Induction of differentiate into odontogenic cells from murine embryonic stem cell

我们在P0-Cre小鼠和Rosa26R小鼠身上发现，成牙本质细胞是从神经脊细胞分化而来的。在这些小鼠中，神经脊细胞很容易被检测到是LacZ细胞，这些小鼠使我们能够在体内分离LacZ神经脊细胞。此外，我们还发现，在磨牙器官培养中，BMP信号对于磨牙尖的形成是重要的。我们还建立了胚胎干细胞的培养体系，以诱导破骨细胞和成骨细胞分化。结果表明：1)利用P0-cre小鼠和Rosa26R小鼠，神经脊细胞及其后代可以很容易地被检测到是LacZ细胞，并可以被分离出来。胚胎胸腺中存在具有向黑素细胞和神经细胞分化潜能的多能神经脊细胞。2)在牙齿器官培养中，利用可溶性形成的BMP I型受体抑制BMP信号，E13.5和E16.5牙蕾BMP信号的抑制导致异常牙尖的形成。这些结果表明，BMP信号对牙齿形态发生的各个阶段的牙尖形成是必不可少的。3)我们建立了胚胎干细胞的培养体系，以诱导破骨细胞和成骨细胞的分化。我们已经发表了论文3)，稿件1)2)已经提交。最近，我们建立了黑素细胞的培养体系，黑素细胞来源于神经脊细胞，来源于小鼠胚胎干细胞。此外，我们还建立了在成牙本质细胞中特异表达LacZ的DSP-LacZ小鼠。因此，我们有可能建立胚胎干细胞向成牙本质细胞分化的新体系。

We have found that odontoblasts are derived from neural crest cells using P0-cre mice and Rosa26R mice. In these mice, neural crest cells are easily detected as LacZ+ cells and these mice enable us to isolate LacZ+ neural crest cells in vivo. Furthermore, we have found that BMP signalings are important for molar cusp formation in tooth molar organ culture. We also developed the culture system of embryonic stem cells to induce the differentiation of osteoclasts and osteoblasts. The results are shown as follows.1) Using P0-cre mice and Rosa26R mice, neural crest cells and their progeny can be easily detected as LacZ+ cells and can be isolated. Multipotent neural crest cells with a potential of differentiate into melanocyte and neuroal cells were present in the fetal thymus.2) Using soluble formed BMP type I receptor to inhibit BMP signaling in tooth organ culture, the inhibition of BMP signaling at both E13.5 and E16.5 tooth buds leads to abnormal cusp formation. These results indicate that BMP signaling is essential for the proper cusp formation in all stags of tooth morphogenesis.3) We developed the culture system of embryonic stem cells to induce the differentiation of osteoclasts and osteoblasts.We have already published the papers 3) and the manuscripts 1) 2) have been submitted. Recently, we established the culture system of melanocytes, which are derived from neural crest cells are induced from murine embryonic stem cells. Furthermore, we also established the Dsp-LacZ mice, which expressed LacZ in odontoblast specially. Therefore, we may establish new system of differentiation into odontoblast from embryonic stem cell through neural crest cells.