Temporal migration of gonadotrophin-releasing hormone-1 neurones is modified in GAD67 knockout mice.
Gonadotrophin-releasing hormone (GnRH-1) neurones reside in the forebrain and regulate gonadal function via the hypothalamic-pituitary-gonadal axis. Disruption of this axis results in reproductive dysfunction. During embryonic development, GnRH-1 neurones migrate from the nasal pit through the nasal/forebrain junction (NFJ) into the developing brain. Prenatally gamma-aminobutyric acid (GABA) is excitatory and has been shown to play a role in nervous system development. Both in vivo and in vitro experiments suggest that GABA inhibits migration of GnRH-1 neurones. The present study examines the migration of GnRH-1 neurones in GAD67 knockout (KO) mice to further elucidate the role of GABA on GnRH-1 neuronal development. Three stages were examined, embryonic day (E)12.5, E14.5 and E17.5. GnRH-1 cell number and location were analysed by immunocytochemistry and in situ hybridisation histochemistry. The total number of GnRH-1 immunopositive cells was similar between wild-type (WT) and KO mice. However, significant differences were found in the overall distribution of GnRH-1 immunopositive cells in GAD67 KO compared to WT mice at all stages. Subsequent analysis by area revealed differences occurred at the NFJ with an increase in GnRH-1 cells in GAD67 KO at E14.5 and a decrease in GnRH-1 cells in GAD67 KO at E17.5. Comparable counts for cells expressing GnRH-1 transcript and protein were obtained. These data indicate that attenuated levels of GABA accelerate GnRH-1 cell migration in nasal areas as well as movement of GnRH-1 cells into the central nervous system at the NFJ.
Lee
J M
JM
Cellular and Developmental Neurobiology Section, National Institute of Neurological Disorder and Stroke, National Institutes of Health, Bethesda, MD, USA.
Tiong
J
J
Maddox
D M
DM
Condie
B G
BG
Wray
S
S
D000818:Animals; D002465:Cell Movement / Q000235:genetics*; D004622:Embryo, Mammalian; D005968:Glutamate Decarboxylase / Q000235:genetics* / Q000502:physiology; D007987:Gonadotropin-Releasing Hormone / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D008954:Models, Biological; D009297:Nasal Mucosa / Q000378:metabolism; D009474:Neurons / Q000378:metabolism / Q000502:physiology*; D009666:Nose / Q000196:embryology; D016548:Prosencephalon / Q000196:embryology / Q000378:metabolism
D007987:Gonadotropin-Releasing Hormone; D005968:Glutamate Decarboxylase; C402565:glutamate decarboxylase 1