Differential modulation of proliferation in the neocortical ventricular and subventricular zones.
Recent studies have implicated the classical neurotransmitters GABA and glutamate in the regulation of neural progenitor proliferation. We now show that GABA and glutamate have opposite effects on the two neural progenitor populations in the ventricular zones (VZs) and subventricular zones (SVZs) of the embryonic cerebrum. Application of either molecule to organotypic slice cultures dramatically increases proliferation in the VZ by shortening the cell cycle, whereas proliferation in the SVZ is decreased. These disparate effects, measured both by bromodeoxyuridine uptake and the expansion of retrovirally labeled progenitor clones, are mimicked by the application of specific GABA and glutamate agonists and are blocked by antagonists. Thus, the relative contributions of the VZ and SVZ to neocortical growth may be regulated by differential responsiveness to GABA and glutamate.
Haydar
T F
TF
Section of Neurobiology, Yale University School of Medicine, New Haven, CT 06510, USA.
Wang
F
F
Schwartz
M L
ML
Rakic
P
P
D018750:6-Cyano-7-nitroquinoxaline-2,3-dione / Q000494:pharmacology; D000818:Animals; D000963:Antimetabolites / Q000494:pharmacology; D001973:Bromodeoxyuridine / Q000494:pharmacology; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology; D002455:Cell Division / Q000187:drug effects / Q000502:physiology; D002465:Cell Movement / Q000187:drug effects / Q000502:physiology; D002552:Cerebral Ventricles / Q000737:chemistry / Q000166:cytology* / Q000196:embryology; D002999:Clone Cells / Q000187:drug effects / Q000502:physiology; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D005333:Fetus / Q000166:cytology; D018755:GABA Agonists / Q000494:pharmacology; D018756:GABA Antagonists / Q000494:pharmacology; D018698:Glutamic Acid / Q000032:analysis / Q000494:pharmacology*; D007608:Kainic Acid / Q000494:pharmacology; D051379:Mice; D008813:Mice, Inbred ICR; D009118:Muscimol / Q000494:pharmacology; D019579:Neocortex / Q000737:chemistry / Q000166:cytology* / Q000196:embryology; D009474:Neurons / Q000166:cytology*; D009924:Organ Culture Techniques; D013234:Stem Cells / Q000166:cytology* / Q000187:drug effects; D005680:gamma-Aminobutyric Acid / Q000032:analysis / Q000494:pharmacology*
D000963:Antimetabolites; D018690:Excitatory Amino Acid Agonists; D018691:Excitatory Amino Acid Antagonists; D018755:GABA Agonists; D018756:GABA Antagonists; D009118:Muscimol; D018698:Glutamic Acid; D005680:gamma-Aminobutyric Acid; D018750:6-Cyano-7-nitroquinoxaline-2,3-dione; D001973:Bromodeoxyuridine; D007608:Kainic Acid