Transcriptional regulation for mesenchymal defferentiation in mouse embryonal mandibular process

尽管先前报道与软骨分化和发育相关的因子是胚胎形态发生期间下颌突中的生长因子如EGF和/或FGF-α，本研究提示，Msx 2的一种转录调节因子，即细胞生长抑制因子，在软骨形成和软骨分化过程中也具有抑制作用，与Sox 9的拮抗作用密切相关。在本研究中，我们有一个假设，几个发展事件是协同控制的系统机制。这些是发育事件的位置重叠的几个证据，例如牙齿位置的确定是由上皮中的BMP 4和FGF 8以及间质中的Pax 9的协同和拮抗功能决定的。下颌突空间位置的起始与下颌突软骨形成机制密切相关。此外，我们研究了舌肌细胞分化，并报道TGF-α增加MyoD和myogenin的表达。这表明生长因子不仅促进细胞生长，而且促进细胞分化。Msx 2在舌发育过程中也有表达，但其空间特异性和生长调控机制尚不清楚，其协同系统机制的挑战性问题和假说有待于通过详细观察多种转录调控因子在下颌突发育过程中的时空表达模式来解决。还需要克服本研究不能完全控制的器官培养体系中基因表达调控的技术程序。在这一领域的进一步改进和挑战将在未来完成。

Although the factors related with the differentiation and development of cartilage are previously reported as growth factors such as EGF and/or FGF-a in the mandibular process during embryonal morphogenesis, the genetic regulation mechanisms of the growth factors are little known.The present study suggest a transcriptional regulating factor of Msx2 that are known as a cell growth inhibitory factor reveals also inhibitory function during the chondrogenesis and the function is closely related with Sox9 antagonistically. In the present study, we have a hypothesis that several developmental events are synergistically controlled by a systemic mechanism. These are several evidences of positional overlap of developmental event such as the determination of tooth position that determined by co-operative and antagonistic function of BMP4 and FGF8 in epithelium and Pax9 in mesenchym. The initiation of spatial position in mandibular process is closely related with the mechanisms of chondrogenesis in the mandibular process synergistically.Furthermore, we examined muscular cell differentiation in the tongue and reported that TGF-a increase expression of MyoD and myogenin. This suggest the growth factor promote not only cell growth but also cell differentiation. Msx2 is also expressed during the tongue development, however, the spatial specificity and growth control mechanism of the muscle cells are still unclear.The challenging problems and hypothesis of the synergistic systemic mechanisms are should be resolved by detailed observation for expression pattern of many transcriptional regulating factors in the mandibular process in spatial and temporal developmental stages. It should be also overcome the technical procedures for gene expression control in the organ culture system that could not completely controlled in this study. Further improvements and challenges in this field will be done in future.