Nitric oxide is an essential negative regulator of cell proliferation in Xenopus brain

N Peunova; V Scheinker; H Cline; G Enikolopov

doi:10.1523/JNEUROSCI.21-22-08809.2001

Nitric oxide is an essential negative regulator of cell proliferation in Xenopus brain

J Neurosci. 2001 Nov 15;21(22):8809-18. doi: 10.1523/JNEUROSCI.21-22-08809.2001.

Authors

N Peunova¹, V Scheinker, H Cline, G Enikolopov

Affiliation

¹ Cold Spring Harbor Laboratory, Cold Spring Harbor, New York 11724, USA. peunova@cshl.org

Abstract

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.

Publication types

Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.
Research Support, U.S. Gov't, P.H.S.

MeSH terms

Animals
Apoptosis / drug effects
Brain / cytology
Brain / drug effects
Brain / growth & development
Brain / metabolism*
Bromodeoxyuridine
Cell Count
Cell Differentiation / drug effects
Cell Differentiation / physiology
Cell Division / drug effects
Cell Division / physiology
Cell Size / drug effects
Drug Implants
Enzyme Inhibitors / pharmacology
In Situ Hybridization
Larva
Molecular Sequence Data
Morphogenesis / drug effects
Neurons / cytology
Neurons / drug effects
Neurons / metabolism
Nitric Oxide / metabolism*
Nitric Oxide / pharmacology
Nitric Oxide Donors / pharmacology
Nitric Oxide Synthase / antagonists & inhibitors
Nitric Oxide Synthase / genetics
Nitric Oxide Synthase / metabolism*
Nitric Oxide Synthase Type I
Organ Specificity
Xenopus

Substances

Drug Implants
Enzyme Inhibitors
Nitric Oxide Donors
Nitric Oxide
Nitric Oxide Synthase
Nitric Oxide Synthase Type I
Bromodeoxyuridine