Molecular machanism of the MFH-1 gene in, the aoortic arch formation, Skeletogenesis and kidney formation

MFH-1基因在主动脉弓形成、骨骼发生和肾脏形成中的分子机制

基本信息

批准号：
11694239
负责人：
MIURA Naoyuki
金额：
$ 5.89万
依托单位：
Hamamatsu University School of Medicine
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B)
财政年份：
1999
资助国家：
日本
起止时间：
1999 至 2001
项目状态：
已结题

项目摘要

In the first year we investigated the relationship between the MFH-1 and Pax1 genes in skeletogenesis. We obtained the results that MFH-1 and Pax1 were expressed in the ventral and lateral areas of sclerotome and that MFH-1 expression is dependent on the notochord. We also investigated that the MFH-1/Pax1 double knockout mice showed more severe defects in cell proliferative ability in the sclerotomal cells than either single knockout mouse did.These results showed that MFH-1 and Pax1 play a cooperative role in the sclerotome to make vertebraes. In the second year, we investigated the relationship between the MFH-1 and endothelin receptor A (ETA) genes in the aortic arch formation. The results that MFH-1 and ETA were expressed at the similar areas and at similar time and that both knockout mice showed interrupted aortic arch seem likely that there is an upstream-down stream relationship between these two genes. However, the in situ hybridization experiments using the knockout mice indicated that MFH-1 and ETA might act independently in the aortic arch formation. In the last year, we investigated the phenotypes of MFH 1/ETA double knockout mice. We found that the double knockout mice died at the embryonic day of 11.5 day due to heart failure. In the study on the role of MFH-1 gene in the bone differentiation, we found that the MFH-1 gene was expressed strongly just before the bone formation and its expression decreased after the bone was differentiated. Next, we determined whether the MFH-1 gene was induced in response to the implanted beads containing the bone morphogenetic protein (BMP) in the developing mouse limbs. The result showed that the MFH-1 expression was enhanced at a little remote site from the beads. The data together indicate that BMP regulates the MFH-1 gene directly or indirectly in the bone formation of mouse limbs.

第一年，我们研究了 MFH-1 和 Pax1 基因在骨骼发生中的关系。我们得到的结果是，MFH-1和Pax1在巩膜的腹侧和侧部区域表达，并且MFH-1的表达依赖于脊索。我们还研究发现，MFH-1/Pax1双敲除小鼠的巩膜细胞中细胞增殖能力的缺陷比单敲除小鼠更严重。这些结果表明，MFH-1和Pax1在巩膜细胞中发挥协同作用，使椎骨。第二年，我们研究了 MFH-1 和内皮素受体 A (ETA) 基因在主动脉弓形成中的关系。 MFH-1和ETA在相似的区域和相似的时间表达，并且两只敲除小鼠都显示出中断的主动脉弓，这似乎表明这两个基因之间存在上下游关系。然而，使用敲除小鼠进行的原位杂交实验表明，MFH-1和ETA可能在主动脉弓形成中独立发挥作用。去年，我们研究了MFH 1/ETA双敲除小鼠的表型。我们发现双基因敲除小鼠在胚胎第11.5天就因心力衰竭而死亡。在研究MFH-1基因在骨分化中的作用时，我们发现MFH-1基因在骨形成前强烈表达，在骨分化后表达减弱。接下来，我们确定了在发育中的小鼠四肢中植入的含有骨形态发生蛋白（BMP）的珠子是否会诱导 MFH-1 基因的产生。结果表明，在距离珠稍远的位点，MFH-1表达增强。这些数据共同表明BMP在小鼠四肢的骨形成中直接或间接调节MFH-1基因。