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)已知间充质细胞既来源于神经脊细胞，也来源于中胚层。尤其是在包括牙间充质在内的颅面部，神经脊起着重要的作用。在PO-Cre/Rosa26R小鼠体内示踪NC来源的细胞为LacZ^+细胞，发现大量NC来源的细胞提供牙本质间充质，NC来源的牙间充质分化为成牙本质细胞、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来源的细胞都参与了牙间充质的形成。2)用Mespl-cre/Rosa26R小鼠示踪中胚层来源的细胞为LacZ^+细胞，发现中胚层来源的细胞参与了牙间充质的形成。3)我们在PO-Cre/Rosa26R小鼠身上发现，参与胸腺器官发生的NC来源的细胞具有向黑素细胞、神经元和神经胶质细胞分化的潜力。我们认为NC和非NC去细胞在使用这些小鼠的胸腺间充质中都有贡献(Yamazaki，2005)。4)我们通过神经脊特异性基因的表达证明了神经脊中N-rasG12V的表达特异性地促进了神经纤维瘤病的表现(Saito，2007)。5)我们建立了小鼠胚胎干细胞的NC来源的黑素细胞的培养体系。利用内皮素3或c-Kit干扰ES细胞，我们证明了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ES细胞培养成某些谱系时，很难避免不良谱系细胞。我们发现，PU1的增强表达可以从缺乏TAL-1的ES细胞中拯救破骨细胞的形成，因为ES细胞不能分化为造血细胞。因此，我们可能会使用这些系统来调节ES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)