Cox Eric, Lanier Jason, Quina Lely, Eng S Raisa, Turner Eric E
Department of Psychiatry, University of California, San Diego and VA San Diego Healthcare System, La Jolla, California 92093, USA.
J Neurobiol. 2006 Sep 1;66(10):1075-83. doi: 10.1002/neu.20277.
The POU-domain transcription factor Brn3a is expressed in specific neurons of the caudal CNS and peripheral sensory nervous system. The sensory neurons of mice lacking Brn3a exhibit marked defects in axon growth and extensive apoptosis in late gestation. Here we show that expression of the developmental regulator FGF10 is approximately 35-fold increased in the developing trigeminal ganglia of Brn3a-null mice. In order to determine whether FGF10 regulates other changes in gene expression observed in Brn3a knock-out ganglia, we have used a sensory-specific enhancer to over-express FGF10 in transgenic mice. Microarray analysis of trigeminal ganglia from individual transgenic founders effectively excludes the cell-autonomous activity of FGF10 as a mechanism for mediating the downstream effects of the loss of Brn3a, probably because developing sensory neurons lack the appropriate type of FGF receptor.
POU 结构域转录因子 Brn3a 在尾侧中枢神经系统和外周感觉神经系统的特定神经元中表达。缺乏 Brn3a 的小鼠的感觉神经元在轴突生长方面表现出明显缺陷,并且在妊娠后期出现广泛的细胞凋亡。在此我们表明,发育调节因子 FGF10 在 Brn3a 基因敲除小鼠发育中的三叉神经节中的表达增加了约 35 倍。为了确定 FGF10 是否调节在 Brn3a 基因敲除神经节中观察到的基因表达的其他变化,我们使用了一种感觉特异性增强子在转基因小鼠中过表达 FGF10。对单个转基因创始人的三叉神经节进行微阵列分析有效地排除了 FGF10 的细胞自主活性作为介导 Brn3a 缺失的下游效应的机制,这可能是因为发育中的感觉神经元缺乏适当类型的 FGF 受体。