Chung Il-Hyuk, Han Jun, Iwata Junichi, Chai Yang
Center for Craniofacial Molecular Biology, Ostrow School of Dentistry, University of Southern California, Los Angeles, California 90033, USA.
Genesis. 2010 Nov;48(11):645-55. doi: 10.1002/dvg.20671. Epub 2010 Nov 2.
The Msx and Dlx families of homeobox proteins are important regulators for embryogenesis. Loss of Msx1 in mice results in multiple developmental defects including craniofacial malformations. Although Dlx5 is widely expressed during embryonic development, targeted null mutation of Dlx5 mainly affects the development of craniofacial bones. Msx1 and Dlx5 show overlapping expression patterns during frontal bone development. To investigate the functional significance of Msx1/Dlx5 interaction in regulating frontal bone development, we generated Msx1 and Dlx5 double null mutant mice. In Msx1(-/-) ;Dlx5(-/-) mice, the frontal bones defect was more severe than that of either Msx1(-/-) or Dlx5(-/-) mice. This aggravated frontal bone defect suggests that Msx1 and Dlx5 function synergistically to regulate osteogenesis. This synergistic effect of Msx1 and Dlx5 on the frontal bone represents a tissue specific mode of interaction of the Msx and Dlx genes. Furthermore, Dlx5 requires Msx1 for its expression in the context of frontal bone development. Our study shows that Msx1/Dlx5 interaction is crucial for osteogenic induction during frontal bone development.
同源盒蛋白的Msx和Dlx家族是胚胎发育的重要调节因子。小鼠中Msx1的缺失会导致多种发育缺陷，包括颅面畸形。尽管Dlx5在胚胎发育过程中广泛表达，但Dlx5的靶向无效突变主要影响颅面骨的发育。Msx1和Dlx5在额骨发育过程中表现出重叠的表达模式。为了研究Msx1/Dlx5相互作用在调节额骨发育中的功能意义，我们构建了Msx1和Dlx5双缺失突变小鼠。在Msx1(-/-);Dlx5(-/-)小鼠中，额骨缺陷比Msx1(-/-)或Dlx5(-/-)小鼠更严重。这种加重的额骨缺陷表明Msx1和Dlx5协同作用来调节成骨作用。Msx1和Dlx5对额骨的这种协同作用代表了Msx和Dlx基因相互作用的一种组织特异性模式。此外，在额骨发育的背景下，Dlx5的表达需要Msx1。我们的研究表明，Msx1/Dlx5相互作用对于额骨发育过程中的成骨诱导至关重要。
