Voltage-gated calcium channels in developing GnRH-1 neuronal system in the mouse.
Migration of gonadotropin-releasing hormone-1 (GnRH-1) neurons from the nasal placode into the central nervous system occurs in all vertebrates. This study characterizes the expression of L- and N-type voltage-gated calcium channels (VGCCs) in migrating GnRH-1 neurons in mice. Class C (L-type) and class B (N-type) VGCGs were detected in GnRH-1 cells and cells in the olfactory and vomeronasal epithelium during prenatal development. This expression pattern was mimicked in a nasal explant model known to retain many characteristics of GnRH-1 development in vivo. Using this in vitro system, perturbation studies were performed to elucidate the role of VGCCs in GnRH-1 neuronal development. This report shows that olfactory axon outgrowth and GnRH-1 neuronal migration are attenuated when nasal explants are grown in calcium-free media, and that this effect is temporally restricted to an early developmental period. Blockade of either the L- or the N-type channel did not alter GnRH-1 cell number or overall olfactory axon outgrowth. However, blockade of N-type channels altered the distribution of GnRH-1 neurons in the periphery of the nasal explants. In these explants, more GnRH-1 neurons were located proximal to, and fewer GnRH-1 neurons distal to, the main tissue mass, suggesting a general decrease in the rate of GnRH-1 neuronal migration. These results indicate that extracellular calcium is required for initiating GnRH-1 neuronal migration and that these events are partially dependent on N-type VGCC signals.
Toba
Yoko
Y
Cellular and Developmental Neurobiology Section, NINDS, NIH, Bethesda, MD 20892, USA.
Pakiam
Jennifer G
JG
Wray
Susan
S
D000818:Animals; D001921:Brain / Q000166:cytology / Q000196:embryology / Q000378:metabolism; D002118:Calcium / Q000172:deficiency; D002121:Calcium Channel Blockers / Q000494:pharmacology; D015220:Calcium Channels / Q000187:drug effects / Q000378:metabolism*; D020746:Calcium Channels, L-Type / Q000187:drug effects / Q000378:metabolism; D020864:Calcium Channels, N-Type / Q000187:drug effects / Q000378:metabolism; D002452:Cell Count; D002454:Cell Differentiation / Q000502:physiology*; D002465:Cell Movement / Q000502:physiology*; D045604:Extracellular Fluid / Q000187:drug effects / Q000378:metabolism; D007987:Gonadotropin-Releasing Hormone / Q000378:metabolism*; D020439:Growth Cones / Q000378:metabolism; D051379:Mice; D009474:Neurons / Q000166:cytology / Q000378:metabolism*; D009831:Olfactory Mucosa / Q000166:cytology / Q000196:embryology* / Q000378:metabolism; D009924:Organ Culture Techniques; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology
D002121:Calcium Channel Blockers; D015220:Calcium Channels; D020746:Calcium Channels, L-Type; D020864:Calcium Channels, N-Type; D007987:Gonadotropin-Releasing Hormone; D002118:Calcium