Reynolds Annie, Brustein Edna, Liao Meijiang, Mercado Adriana, Babilonia Elisa, Mount David B, Drapeau Pierre
Department of Pathology and Cell Biology and Le Groupe de Recherche sur le Système Nerveux Central, Université de Montréal, Montréal, Québec, Canada H3T 1J4.
J Neurosci. 2008 Feb 13;28(7):1588-97. doi: 10.1523/JNEUROSCI.3791-07.2008.
GABA- and glycine-induced depolarization is thought to provide important developmental signals, but the role of the underlying chloride gradient has not been examined from the onset of development. We therefore overexpressed globally the potassium-chloride cotransporter 2 (KCC2) in newly fertilized zebrafish embryos to reverse the chloride gradient. This rendered glycine hyperpolarizing in all neurons, tested at the time that motor behaviors (but not native KCC2) first appear. KCC2 overexpression resulted in fewer mature spontaneously active spinal neurons, more immature silent neurons, and disrupted motor activity. We observed fewer motoneurons and interneurons, a reduction in the elaboration of axonal tracts, and smaller brains and spinal cords. However, we observed no increased apoptosis and a normal complement of sensory neurons, glia, and progenitors. These results suggest that chloride-mediated excitation plays a crucial role in promoting neurogenesis from the earliest stages of embryonic development.
γ-氨基丁酸（GABA）和甘氨酸诱导的去极化被认为可提供重要的发育信号，但尚未从发育起始阶段对潜在氯离子梯度的作用进行研究。因此，我们在刚受精的斑马鱼胚胎中整体过表达氯化钾协同转运蛋白2（KCC2），以逆转氯离子梯度。这使得甘氨酸在首次出现运动行为（而非天然KCC2）时对所有测试神经元产生超极化作用。KCC2过表达导致成熟的自发活动脊髓神经元数量减少，未成熟的沉默神经元增多，且运动活动受到破坏。我们观察到运动神经元和中间神经元数量减少，轴突束的精细度降低，大脑和脊髓变小。然而，我们未观察到凋亡增加，感觉神经元、神经胶质细胞和祖细胞的数量正常。这些结果表明，氯离子介导的兴奋在胚胎发育的最早阶段促进神经发生过程中起着关键作用。
