Analysis of potential for differentiation of murine neural-crest derived cells in developing teeth and regeneration of hard tissues using their neural-crest derived cells.

1)间充质细胞来源于神经嵴细胞（NC）和中胚层细胞。神经嵴对颅面及牙间质的影响尤为显著。我们利用PO-Cre/Rosa26R小鼠将NC来源的细胞追踪为LacZ^+细胞，发现大量NC来源的牙间质分化为成牙细胞、软骨细胞样细胞和成骨细胞样细胞。（Yamazaki, 2007）此外，我们认为nc来源的细胞和非nc来源的细胞都对牙间质有贡献。2)利用Mespl-cre/Rosa26Rmice将中胚层来源的细胞追踪为LacZ^+细胞，发现中胚层来源的细胞对牙间质有贡献。3)在PO-Cre/Rosa26R小鼠实验中，我们发现参与胸腺器官发生的nc来源细胞具有向黑色素细胞、神经元和胶质细胞分化的潜力。我们认为NC和非NC来源的细胞都对这些小鼠胸腺的间质有贡献（Yamazaki,2005）。4)通过神经嵴特异性基因表达，我们发现N-rasG12V在神经嵴中的表达可特异性促进神经纤维瘤病的表现（Saito, 2007）。5)建立小鼠胚胎干细胞源性黑素细胞培养体系。利用内皮素3或c-Kit干扰胚胎干细胞，我们发现了c-Kit和内皮素3在黑素细胞发育中的作用（Aoki, 2005）。6)当我们将胚胎干细胞培养到某些谱系时，很难避免不良的谱系细胞。我们发现，在缺乏tal-1的胚胎干细胞中，PU.1的强制表达可以促进破骨细胞的形成，而这些细胞不能分化为造血细胞。因此，我们可以利用这些系统调节胚胎干细胞的分化潜能。(Tsuneto, 2005)

1) It is known that mesenchymal cells are derived from both neural crest (NC) cells and mesoderm. Especially, neural crest contributed in cranio-face including dental mesenchyme. By tracing NC-derived cells as LacZ^+ cells using PO-Cre/Rosa26R mice, we found that large numbers of NC cells contributed dental mesenchyme and their NC-derived dental mesenchyme differentiated into odontoblasts, chondrocyte-like cells and osteoblast-like cells. (Yamazaki, 2007) Furthermore, we suggested that both NC-derived cells and non-NC-derived cells contributed in dental mesenchyme. 2) By tracing mesoderm-derived cells as LacZ^+ cells using Mespl-cre/Rosa26Rmice, we found that mesoderm-derived cells contributed in dental mesenchyme. 3) We found that NC-derived cells that participated in thymic organogenesis had a potential to differentiate into melanocytes and neuron and glia using PO-Cre/Rosa26R mice. We suggested that both NC and non-NC derved cells contributed in the mesenchyme of the thymususing these mice (Yamazaki,2005). 4) We showed that N-rasG12V expression in neural crest specifically promoted manifestations of neurofibromatosis using neural crest specific gene expression (Saito, 2007).5) We established culture system of NC-derived melanocytes from murine embryonic stem (ES) cells. Using endothelin3 or c-Kit disrupted ES cells, we showed that the role of c-Kit and endothelin3 in melanocyte development (Aoki, 2005).6) It is difficult to avoid undesirable lineages cells when we culture ES cells into some lineages. We showed that enforced expression of PU.1 rescues osteoclastogenesis from ES cells lacking tal-1 that can not differentiate into hematopoietic cells. Therefore, we might regulate the potential for differentiation of ES cells using these systems. (Tsuneto, 2005)