Serotonin promotes G(o)-dependent neuronal migration in Caenorhabditis elegans.
BACKGROUND
The directed migration of neurons during development requires attractive and repulsive cues that control the direction of migration as well as permissive cues that potentiate cell motility and responsiveness to guidance molecules.


RESULTS
Here, we show that the neurotransmitter serotonin functions as a permissive signal for embryonic and postembryonic neuronal migration in the nematode C. elegans. In serotonin-deficient mutants, the migrations of the ALM, BDU, SDQR, and AVM neurons were often foreshortened or misdirected, indicating a serotonin requirement for normal migration. Moreover, exogenous serotonin could restore motility to AVM neurons in serotonin-deficient mutants as well as induce AVM-like migrations in the normally nonmotile neuron PVM; this indicates that serotonin was functioning as a permissive cue to enable neuronal motility. The migration defects of serotonin-deficient mutants were mimicked by ablations of serotonergic neuroendocrine cells, implicating humoral release of serotonin in these processes. Mutants defective in G(q) and G(o) signaling, or in N-type voltage-gated calcium channels, showed migration phenotypes similar to serotonin-deficient mutants, and these molecules appeared to genetically function downstream of serotonin in the control of neuronal migration.


CONCLUSIONS
Thus, serotonin is important for promoting directed neuronal migration in the developing C. elegans nervous system. We hypothesize that serotonin may promote cell motility through G protein-dependent modulation of voltage-gated calcium channels in the migrating cell.
Kindt
Katie S
KS
Division of Biological Sciences, University of California, San Diego, La Jolla, CA 92093-0349, USA.
Tam
Tobey
T
Whiteman
Shaleah
S
Schafer
William R
WR
D000818:Animals; D017173:Caenorhabditis elegans / Q000502:physiology*; D029742:Caenorhabditis elegans Proteins / Q000187:drug effects / Q000235:genetics / Q000502:physiology; D002465:Cell Movement / Q000187:drug effects; D019206:GTP-Binding Protein alpha Subunits, Gi-Go; D005838:Genotype; D020962:Heterotrimeric GTP-Binding Proteins / Q000187:drug effects / Q000502:physiology*; D008959:Models, Neurological; D016296:Mutagenesis; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D012701:Serotonin / Q000172:deficiency / Q000494:pharmacology* / Q000502:physiology
D029742:Caenorhabditis elegans Proteins; D012701:Serotonin; D019206:GTP-Binding Protein alpha Subunits, Gi-Go; D020962:Heterotrimeric GTP-Binding Proteins