Loss of Hoxb8 alters spinal dorsal laminae and sensory responses in mice
Loss of Hoxb8 alters spinal dorsal laminae and sensory responses in mice
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DOI：
10.1073/pnas.0802176105
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发表时间：
2008-04-29
影响因子：
11.1
通讯作者：
Deschamps, Jacqueline
中科院分区：
文献类型：
--
作者：
Holstege, Jan C.;Graaff, Wirn Cle;Deschamps, Jacqueline
虽然Hox基因的表达与运动神经元的身份有关，但这些基因在脊髓感觉系统发育中的作用仍然没有文献记载。Hoxb基因在脊髓背角中高水平表达。Hoxb8无效突变体表现出一个惊人的表型过度梳理和无毛病变的下背部。在无毛皮肤下应用局部麻醉抑制了过度梳理，表明这种行为取决于外周神经活动。小鼠Hoxb8的功能性消融也导致对伤害性刺激和热刺激的反应减弱。虽然脊神经节是正常的，有丝分裂后的神经计数较低，被发现在最背侧的椎板在腰部水平的出生，导致一个较小的背角和相应缩小的投射领域的伤害性和热感受性传入。我们检测的背神经元细胞类型的分布，包括表达瘙痒特异性胃泌素释放肽受体的神经元，在突变体的腰部区域是混乱的。BrdU标记实验和这些神经元出生前后各阶段的基因表达研究表明，HoxbB的缺失在大约胚胎日（E）15.5时开始损害腰脊髓上层的发育。因为所使用的神经元标记物在成人背角中均不表达，所以Hoxb8的缺失不会损害神经元分化。因此，这些数据表明，较低数量的神经元在上脊髓板和神经元的解体在背角的感觉缺陷，包括过度梳理的Hoxb8突变体。
Although Hox gene expression has been linked to motoneuron identity, a role of these genes in development of the spinal sensory system remained undocumented. Hoxb genes are expressed at high levels in the dorsal horn of the spinal cord. Hoxb8 null mutants manifest a striking phenotype of excessive grooming and hairless lesions on the lower back. Applying local anesthesia underneath the hairless skin suppressed excessive grooming, indicating that this behavior depends on peripheral nerve activity. Functional ablation of mouse Hoxb8 also leads to attenuated response to nociceptive and thermal stimuli. Although spinal ganglia were normal, a lower postmitotic neural count was found in the dorsal-most laminae at lumbar levels around birth, leading to a smaller dorsal horn and a correspondingly narrowed projection field of nociceptive and thermoceptive afferents. The distribution of the dorsal neuronal cell types that we assayed, including neurons expressing the itch-specific gastrin-releasing peptide receptor, was disorganized in the lumbar region of the mutant. BrdU labeling experiments and gene-expression studies at stages around the birth of these neurons suggest that loss of HoxbB starts impairing development of the upper laminae of the lumbar spinal cord at approximately embryonic day (E)15.5. Because none of the neuronal markers used was unexpressed in the adult dorsal horn, absence of Hoxb8 does not impair neuronal differentiation. The data therefore suggest that a lower number of neurons in the upper spinal laminae and neuronal disorganization in the dorsal horn underlie the sensory defects including the excessive grooming of the Hoxb8 mutant.