Developmental appearance of cyclic guanosine monophosphate (cGMP) production and nitric oxide responsiveness in embryonic mouse cortex and striatum.
The second messenger cyclic guanosine monophosphate (cGMP) regulates multiple aspects of both structural development and physiological function in the developing nervous system. Recent in vitro experiments have shown that cGMP also modulates the response of developing vertebrate neurons to guidance molecules. This has led to the proposal that in vivo cGMP plays a critical role in directing the outgrowth of the apical dendrites of developing neurons in the cerebral cortex. Despite this proposed role, the onset, localization, and dynamics of cGMP production in the embryonic cortex are unknown. To investigate the potential contribution of cGMP in the embryo, we have used a pharmacological and immunohistochemical approach to test whether the endogenous production of cGMP, and the capacity to produce cGMP in response to nitric oxide (NO), in the cerebral cortex is compatible with the proposed developmental roles for cGMP. We find that cortical cGMP production and NO sensitivity are regionally and developmentally regulated. Cortical cGMP production begins at E15, later than in the ganglionic eminences, becomes high in the cortical plate but not the ventricular zone, and is dependent on nitric oxide synthase activity. Furthermore, although radially migrating neurons were not NO responsive until they reached the cortical plate, NO exposure revealed an additional population of tangentially migrating presumptive interneurons from the ganglionic eminences with the capacity to produce cGMP. These results provide a new level of understanding of the stage and cell type specific regulation of the NO/cGMP pathway during embryonic development.
Currie
Douglas A
DA
Department of Biology, University of Washington, Seattle, Washington, USA. dcurrie@usm.maine.edu
de Vente
Jan
J
Moody
William J
WJ
D000818:Animals; D002540:Cerebral Cortex / Q000166:cytology / Q000196:embryology* / Q000378:metabolism; D003342:Corpus Striatum / Q000196:embryology* / Q000378:metabolism; D006152:Cyclic GMP / Q000096:biosynthesis*; D051379:Mice; D008810:Mice, Inbred C57BL; D009569:Nitric Oxide / Q000502:physiology*
D009569:Nitric Oxide; D006152:Cyclic GMP