Transcriptional regulation for mesenchymal defferentiation in mouse embryonal mandibular process

尽管与软骨分化发育相关的因子在胚胎形态发生过程中被报道为生长因子，如表皮生长因子和/或成纤维细胞生长因子，但这些生长因子的遗传调控机制尚不清楚。本研究提示MSX2的转录调控因子，即细胞生长抑制因子，在软骨形成过程中也具有抑制作用，该作用与Sox9拮抗作用密切相关。在目前的研究中，我们有一个假设，几个发育事件是由一个系统机制协同控制的。这是发育事件位置重叠的几个证据，例如牙齿位置的确定是由上皮细胞中BMP4和FGF8以及间质中Pax9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的协同作用密切相关。此外，我们还检测了舌肌细胞的分化，并报道了转化生长因子-α增加了MyoD和肌肉生成素的表达。这表明生长因子不仅能促进细胞生长，还能促进细胞分化。MSX2在舌体发育过程中也有表达，但肌肉细胞的空间特异性和生长调控机制尚不清楚，协同系统机制的挑战性问题和假说需要通过详细观察多种转录调控因子在下颌突时空发育阶段的表达模式来解决。还应克服本研究中不能完全控制的器官培养系统中基因表达调控的技术程序。今后将在这一领域进行进一步的改进和挑战。

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.