Developmental expression of the calcium release channels during early neurogenesis of the mouse cerebral cortex.
The developmental changes of intracellular calcium release channels of mouse neocortex were studied at the onset of neurogenesis, which occurs between embryonic days E11 and E17. The three main isoforms of the two families of intracellular calcium release channels, namely the inositol trisphosphate receptors (IP3R) and the ryanodine receptors (RyR), were detected by their transcripts in the cerebral hemispheres, as early as stage E11. The major isoforms of each family, IP3R-1 and RyR-2, were found at the protein level by Western blot analysis. Expression of these proteins increases progressively throughout brain development. Their localization in coronal sections of cortex has been observed by immunodetection from E12, and compared to the TuJ1 (anti-class III beta-tubulin antibody) neuronal specific labelling. The expression of both channels is greatly enhanced after E12, and both were seen to be present in most of the proliferative and neuronal cells of the slice. Between E12 and E13, there is a striking transition in the pattern of calcium release elicited by specific agonists of these channels, thimerosal for IP3R and caffeine for RyR. The signals induced by thimerosal were not zone-specific, while the observed calcium release signals induced by caffeine were predominantly restricted out of the ventricular zone. This zone-specific caffeine sensitivity is consistent with the main RyR localization immunodetected at E13. Our results indicate that there is a time lag of several days between the molecular detection of calcium release channels and their functional expression, around the time of neuronal differentiation. Altogether, they provide a molecular basis for analyzing the developmental modulation of calcium signals useful for neurogenesis progression.
Faure
A V
AV
Laboratoire Canaux Ioniques et Signalisation, INSERM E 9931, Département de Biologie Moléculaire et Structurale, 17 rue des Martyrs, F-38054 Grenoble, France.
Grunwald
D
D
Moutin
M J
MJ
Hilly
M
M
Mauger
J P
JP
Marty
I
I
De Waard
M
M
Villaz
M
M
Albrieux
M
M
D000818:Animals; D015153:Blotting, Western; D002110:Caffeine / Q000494:pharmacology; D015220:Calcium Channels / Q000235:genetics / Q000378:metabolism*; D020013:Calcium Signaling / Q000187:drug effects / Q000502:physiology; D002135:Calcium-Binding Proteins / Q000378:metabolism; D037282:Calreticulin; D002454:Cell Differentiation / Q000502:physiology*; D002455:Cell Division / Q000502:physiology*; D000697:Central Nervous System Stimulants / Q000494:pharmacology; D002540:Cerebral Cortex / Q000166:cytology / Q000196:embryology* / Q000378:metabolism; D002614:Chelating Agents / Q000494:pharmacology; D004533:Egtazic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology; D005260:Female; D005333:Fetus; D005455:Fluorescent Antibody Technique; D018507:Gene Expression Regulation, Developmental / Q000502:physiology; D053496:Inositol 1,4,5-Trisphosphate Receptors; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009474:Neurons / Q000166:cytology / Q000378:metabolism*; D011310:Preservatives, Pharmaceutical / Q000494:pharmacology; D020033:Protein Isoforms / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D018160:Receptors, Cytoplasmic and Nuclear / Q000235:genetics / Q000378:metabolism*; D012261:Ribonucleoproteins / Q000378:metabolism; D019837:Ryanodine Receptor Calcium Release Channel / Q000235:genetics / Q000378:metabolism*; D013234:Stem Cells / Q000166:cytology / Q000378:metabolism*; D013849:Thimerosal / Q000494:pharmacology; D014158:Transcription, Genetic / Q000502:physiology; D014404:Tubulin / Q000378:metabolism
D015220:Calcium Channels; D002135:Calcium-Binding Proteins; D037282:Calreticulin; D000697:Central Nervous System Stimulants; D002614:Chelating Agents; D053496:Inositol 1,4,5-Trisphosphate Receptors; D011310:Preservatives, Pharmaceutical; D020033:Protein Isoforms; D012333:RNA, Messenger; D018160:Receptors, Cytoplasmic and Nuclear; D012261:Ribonucleoproteins; D019837:Ryanodine Receptor Calcium Release Channel; D014404:Tubulin; C070379:1,2-bis(2-aminophenoxy)ethane N,N,N',N'-tetraacetic acid acetoxymethyl ester; D013849:Thimerosal; D002110:Caffeine; D004533:Egtazic Acid