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*NITRIC OXIDE

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The Journal of Neuroscience, November 15, 2001, 21(22):8809-8818

Nitric Oxide Is an Essential Negative Regulator of Cell Proliferation in Xenopus Brain

Natalia Peunova, Vladimir Scheinker, Hollis Cline, and Grigori Enikolopov

Cold Spring Harbor Laboratory, Cold Spring Harbor, New York 11724

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.

Key words: nitric oxide; Xenopus; differentiation; proliferation; brain; optic tectum; neuron; neuronal precursors


Copyright © 2001 Society for Neuroscience  0270-6474/01/21228809-10$05.00/0


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