Nitric oxide is an essential negative regulator of cell proliferation in Xenopus brain.
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.
Peunova
N
N
Cold Spring Harbor Laboratory, Cold Spring Harbor, New York 11724, USA. peunova@cshl.org
Scheinker
V
V
Cline
H
H
Enikolopov
G
G
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001921:Brain / Q000166:cytology / Q000187:drug effects / Q000254:growth & development / Q000378:metabolism*; D001973:Bromodeoxyuridine; D002452:Cell Count; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology; D002455:Cell Division / Q000187:drug effects / Q000502:physiology; D048429:Cell Size / Q000187:drug effects; D004343:Drug Implants; D004791:Enzyme Inhibitors / Q000494:pharmacology; D017403:In Situ Hybridization; D007814:Larva; D008969:Molecular Sequence Data; D009024:Morphogenesis / Q000187:drug effects; D009474:Neurons / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism* / Q000494:pharmacology; D020030:Nitric Oxide Donors / Q000494:pharmacology; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D052248:Nitric Oxide Synthase Type I; D009928:Organ Specificity; D014981:Xenopus
D004343:Drug Implants; D004791:Enzyme Inhibitors; D020030:Nitric Oxide Donors; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; D052248:Nitric Oxide Synthase Type I; D001973:Bromodeoxyuridine