Peunova N, Scheinker V, Cline H, Enikolopov G
Cold Spring Harbor Laboratory, Cold Spring Harbor, New York 11724, USA.
J Neurosci. 2001 Nov 15;21(22):8809-18. doi: 10.1523/JNEUROSCI.21-22-08809.2001.
Mechanisms controlling the transition of a neural precursor cell from proliferation to differentiation during brain development determine the distinct anatomical features of the brain. Nitric oxide (NO) may mediate such a transition, because it can suppress DNA synthesis and cell proliferation. We cloned the gene encoding the neuronal isoform of Xenopus NO synthase (XNOS) and found that in the developing brain of Xenopus tadpoles, a zone of XNOS-expressing cells lies adjacent to the zone of dividing neuronal precursors. Exogenous NO, supplied to the tadpole brain in vivo, decreased the number of proliferating cells and the total number of cells in the optic tectum. Conversely, inhibition of NOS activity in vivo increased the number of proliferating cells and the total number of cells in the optic tectum. NOS inhibition yielded larger brains with grossly perturbed organization. Our results indicate that NO is an essential negative regulator of neuronal precursor proliferation during vertebrate brain development.
在大脑发育过程中，控制神经前体细胞从增殖向分化转变的机制决定了大脑独特的解剖学特征。一氧化氮（NO）可能介导这种转变，因为它可以抑制DNA合成和细胞增殖。我们克隆了非洲爪蟾NO合酶（XNOS）神经元亚型的编码基因，发现在非洲爪蟾蝌蚪发育中的大脑中，表达XNOS的细胞区域与正在分裂的神经前体细胞区域相邻。在体内将外源性NO提供给蝌蚪大脑，可减少视顶盖中增殖细胞的数量和细胞总数。相反，体内抑制NOS活性会增加视顶盖中增殖细胞的数量和细胞总数。NOS抑制导致大脑变大且组织结构严重紊乱。我们的结果表明，NO是脊椎动物大脑发育过程中神经元前体增殖的重要负调节因子。
