Lin Amy W, Carpenter Ellen M
Mental Retardation Research Center, Department of Psychiatry, UCLA School of Medicine, Los Angeles, California 90024, USA.
J Neurobiol. 2003 Sep 15;56(4):328-37. doi: 10.1002/neu.10239.
The paralogous Hox genes Hoxa10 and Hoxd10 are expressed in overlapping domains in the developing lumbar spinal cord and surrounding mesoderm. Independent inactivation of these two genes alters the trajectory of spinal nerves and decreases the complement of motor neurons present in the lumbar spinal cord, whereas dual inactivation of these two genes has been shown to alter peripheral nerve growth and development in the mouse hindlimb. We have examined the organization and distribution of lumbar motor neurons in the spinal cords of Hoxa10/Hoxd10 double mutant animals. Double mutant animals have decreased numbers of lumbar motor neurons in both the medial and lateral motor columns. The anteroposterior position of the lumbar motor column is shifted caudally in double mutant animals, and the distribution of motor neurons is altered across individual spinal segments. Distinctions between classes of motor neurons based on positional specificity appear disrupted in double mutants. Double mutants also demonstrate abnormal spinal cord vasculature and altered kidney placement and size. Our observations suggest that Hoxa10 and Hoxd10 activity is required to specify the position of the lumbar motor column and to provide segmental specification and identity for the lumbar motor neurons.
同源的Hox基因Hoxa10和Hoxd10在发育中的腰脊髓和周围中胚层的重叠区域表达。这两个基因的独立失活会改变脊神经的轨迹，并减少腰脊髓中运动神经元的数量，而这两个基因的双重失活已被证明会改变小鼠后肢周围神经的生长和发育。我们研究了Hoxa10/Hoxd10双突变动物脊髓中腰运动神经元的组织和分布。双突变动物的内侧和外侧运动柱中的腰运动神经元数量均减少。双突变动物中腰运动柱的前后位置向尾侧移动，并且运动神经元在各个脊髓节段中的分布发生改变。基于位置特异性的运动神经元类别之间的差异在双突变体中似乎被破坏。双突变体还表现出异常的脊髓血管系统以及肾脏位置和大小的改变。我们的观察结果表明，需要Hoxa10和Hoxd10的活性来确定腰运动柱的位置，并为腰运动神经元提供节段特异性和特征。
