Rottkamp Catherine A, Lobur Katherine J, Wladyka Cynthia L, Lucky Amy K, O'Gorman Stephen
Department of Neurosciences, Rm E640, Case School of Medicine, Cleveland, OH 44106, USA.
Dev Biol. 2008 Feb 1;314(1):23-39. doi: 10.1016/j.ydbio.2007.10.046. Epub 2007 Nov 12.
The transcription cofactor Pbx3 is critical for the function of hindbrain circuits controlling respiration in mammals, but the perinatal lethality caused by constitutively null mutations has hampered investigation of other roles it may play in neural development and function. Here we report that the conditional loss of Pbx3 function in most tissues caudal to the hindbrain resulted in progressive deficits of posture, locomotion, and sensation that became apparent during adolescence. In adult mutants, the size of the dorsal horn of the spinal cord and the numbers of calbindin-, PKC-gamma, and calretinin-expressing neurons in laminae I-III were markedly reduced, but the ventral cord and peripheral nervous system appeared normal. In the embryonic dorsal horn, Pbx3 expression was restricted to a subset of glutamatergic neurons, but its absence did not affect the initial balance of excitatory and inhibitory interneuron phenotypes. By embryonic day 15 a subset of Meis(+) glutamatergic neurons assumed abnormally superficial positions and the number of calbindin(+) neurons was increased three-fold in the mutants. Loss of Pbx3 function thus leads to the incorrect specification of some glutamatergic neurons in the dorsal horn and alters the integration of peripheral sensation into the spinal circuitry regulating locomotion.
转录辅因子Pbx3对哺乳动物中控制呼吸的后脑回路功能至关重要，但组成型无效突变导致的围产期致死性阻碍了对其在神经发育和功能中可能发挥的其他作用的研究。在此，我们报告，后脑尾部大多数组织中Pbx3功能的条件性缺失导致在青春期出现明显的姿势、运动和感觉进行性缺陷。在成年突变体中，脊髓背角的大小以及I-III层中表达钙结合蛋白、蛋白激酶Cγ和钙视网膜蛋白的神经元数量明显减少，但腹侧脊髓和外周神经系统看起来正常。在胚胎背角中，Pbx3表达局限于谷氨酸能神经元的一个亚群，但其缺失并不影响兴奋性和抑制性中间神经元表型的初始平衡。到胚胎第15天，一部分Meis(+)谷氨酸能神经元占据了异常表浅的位置，并且突变体中钙结合蛋白(+)神经元的数量增加了三倍。因此，Pbx3功能的丧失导致背角中一些谷氨酸能神经元的指定错误，并改变了外周感觉整合到调节运动的脊髓回路中。
