MESODERMAL HOMEODOMAIN PROTEIN DURING VERTEBRA DEVELOPMENT

包裹中枢神经系统的结构-椎骨和 头骨-从体节中胚层和神经嵴发育而来。的 这种发育过程的分子机制还没有 被广泛研究。 我们已经获得了一个小鼠转基因插入 具有以半椎骨为特征的隐性表型的突变， 脊椎融合和颅骨与寰椎融合。我们现在有 确定插入发生在第一个内含子中， 中胚层同源结构域基因MOX 1。 该基因在中胚层中表达为 早在原条阶段和晚在有丝分裂前中胚层， 区分体节和心垫间质，干 动脉和颅面神经嵴。 插入伴随着 通过延伸超过基因的3'末端的缺失。 然而，基因组 含有整个mox 1基因加上另外的3'序列的P1克隆 让我们得以跨越删除因为没有证据表明 染色体区域的额外总体重排或缺失 在插入的周围，很可能表型仅仅是由于 mox 1基因的破坏。 表型与 MOX 1在形成冰前凝析作用中的作用， 相关的同源结构域蛋白，如MOX 2， 表达模式不能补偿MOX 1的损失。 未来的研究将显示mox 1的作用是否主要是在 调节间充质细胞的生长速率，从而指定时间 冷凝点和位置以及骨化的形成 中心，或在指定的身份的附加功能 中轴骨骼的结构。 结果将对 了解小鼠和人类的骨骼和颅骨畸形， 好.

The structures that encase the central nervous system - the vertebra and the skull - develop from somitic mesoderm and from the neural crest. The molecular mechanisms that underlie this developmental process have not been studied widely. We have obtained a murine transgenic insertional mutation with a recessive phenotype characterized by hemivertebrae, vertebral fusions, and fusions between skull and atlas. We now have determined that the insertion occurred in the first intron of the mesodermal homeodomain gene mox1. This gene is expressed in mesoderm as early as the primitive streak stage and later in presomitic mesoderm, differentiating somites, and mesenchyme of the heart cushion, truncus arteriosus and craniofacial neural crest. The insertion was accompanied by a deletion extending beyond the 3' end of the gene. However, genomic P1 clones that contain the entire mox1 gene plus additional 3' sequences have allowed us to span the deletion. Since there is no evidence for additional gross rearrangements or deletions in the chromosomal area surrounding the insertion, it is likely that the phenotype is due solely to the disruption of the mox1 gene. The phenotype is consistent with a role of mox1 in the formation of preskeletal condensations and indicates that related homeodomain proteins such as mox2 with partly overlapping expression patterns are not able to compensate for the loss of mox1. Future studies will show whether the role of mox1 is primarily in regulating growth rates of mesenchymal cells, thus specifying the time points and locations of condensations and the formation of ossification centers, or has additional function in specifying the identity of structures of the axial skeleton. The results will have impact on understanding skeletal and skull malformations in mice and humans as well.