Transcriptional regulation for mesenchymal defferentiation in mouse embryonal mandibular process

虽然在胚胎形态发生过程中，与软骨分化和发育相关的生长因子如EGF和/或FGF-a被报道，但生长因子的遗传调控机制尚不清楚。本研究提示Msx2的一种转录调节因子，即细胞生长抑制因子，在软骨形成过程中也显示出抑制功能，其功能与Sox9具有拮抗关系。在本研究中，我们假设几个发育事件是由一个系统机制协同控制的。这些都是发育事件中位置重叠的证据，如牙齿位置的决定是由上皮中的BMP4和FGF8以及间质中的Pax9的合作和拮抗功能决定的。下颌突空间位置的形成与下颌突软骨形成的机制密切相关。此外，我们检查了舌头的肌肉细胞分化，并报道TGF-a增加了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。Msx2在舌发育过程中也有表达，但其在肌肉细胞中的空间特异性和生长调控机制尚不清楚。对多种转录调节因子在颌骨突发育的时空阶段的表达规律进行详细的观察，可以解决具有挑战性的问题和协同系统机制的假设。还需要克服本研究无法完全控制的器官培养系统基因表达控制的技术程序。这一领域的进一步改进和挑战将在未来进行。

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.