Voltage-dependent -L-type Ca2+ channels participate in regulating neural crest migration and differentiation.
General models of cell activation implicate Ca2+ conductance as pivotal in conveying transmembrane signals. During embryonic development, both cell migration and differentiation are influenced by changes in Ca2+; and, as a consequence, the modulation of Ca2+ is important in the control of many morphogenetic processes. Because Ca2+ conductance may be regulated at voltage-dependent Ca2+ channels (VD-CCs), we investigated whether neural crest cells develop VDCCs and, if so, whether they function in regulating migration and establishing cytomorphology. Autoradiography indicates that neural crest cells in vitro develop -L-type Ca2+ channels during migration and differentiation. Blockage of these channels by verapamil, both in vivo and in vitro, leads to a dramatic and reversible inhibition of neural crest migration. Alterations are manifest in vitro in cell-to-cell and cell-to-substratum contact and in the organization of the actin cytoskeleton. In whole embryos, verapamil or nifedipine inhibits pigment pattern formation. Moreover, blockage of the -L-type Ca2+ channels in whole embryos or cultures, after cells have already migrated and differentiated, results in a significant change in individual cell shape and in the overall pigment cell pattern, suggesting further that maintenance of the differentiated state also requires regulation at the -L-type Ca2+ channel. Since certain aspects of neural crest adhesion and cytoskeletal function are dependent on Ca2+, it is suggested that interactions that regulate the availability of Ca2+ through the VDCC may provide coordinate control of motile and adhesive interactions at the cell-substratum interface.
Moran
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Developmental Biology Laboratory, State University of New York, College at New Paltz 12561.
D000199:Actins / Q000378:metabolism; D000557:Ambystoma / Q000196:embryology; D000818:Animals; D000911:Antibodies, Monoclonal; D001345:Autoradiography; D015220:Calcium Channels / Q000502:physiology*; D002454:Cell Differentiation; D002465:Cell Movement; D002478:Cells, Cultured; D003599:Cytoskeleton / Q000187:drug effects / Q000378:metabolism; D004594:Electrophysiology; D009432:Neural Crest / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D009543:Nifedipine / Q000494:pharmacology; D014018:Tissue Distribution; D014700:Verapamil / Q000494:pharmacology
D000199:Actins; D000911:Antibodies, Monoclonal; D015220:Calcium Channels; D014700:Verapamil; D009543:Nifedipine