Induction of differentiate into odontogenic cells from murine embryonic stem cell

我们用P0-cre小鼠和Rosa26R小鼠发现成牙细胞来源于神经嵴细胞。在这些小鼠中，神经嵴细胞很容易被检测为LacZ+细胞，这些小鼠使我们能够在体内分离LacZ+神经嵴细胞。此外，我们发现BMP信号对磨牙器官培养中磨牙尖的形成很重要。我们还建立了胚胎干细胞诱导破骨细胞和成骨细胞分化的培养体系。结果如下所示。1)使用P0-cre小鼠和Rosa26R小鼠，神经嵴细胞及其后代很容易被检测到为LacZ+细胞，并且可以分离。胎儿胸腺中存在多能神经嵴细胞，具有向黑素细胞和神经细胞分化的潜力。2)利用可溶性形成的BMP I型受体抑制牙器官培养中BMP信号，E13.5和E16.5牙芽中BMP信号的抑制导致牙尖形成异常。这些结果表明，在牙齿形态发生的所有阶段，BMP信号对于牙尖的形成至关重要。3)建立胚胎干细胞诱导破骨细胞和成骨细胞分化的培养体系。我们已经发表了论文，稿子也交上去了。最近，我们建立了由小鼠胚胎干细胞诱导的神经嵴细胞衍生的黑素细胞培养体系。此外，我们还建立了在成牙细胞中特异性表达LacZ的Dsp-LacZ小鼠。因此，我们可以通过神经嵴细胞建立胚胎干细胞向成牙细胞分化的新系统。

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.