Temporal Migration of Gonadotrophin-Releasing Hormone-1 Neurones is Modified in GAD67 Knockout Mice

• Published in: Journal of neuroendocrinology Vol. 20; no. 1; pp. 93 - 103
• Main Authors: Lee, J. M., Tiong, J., Maddox, D. M., Condie, B. G., Wray, S.
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Publishing Ltd 01.01.2008; Blackwell Science
• Subjects: Animals; Biological and medical sciences; Cell Movement - genetics; Embryo, Mammalian; Fundamental and applied biological sciences. Psychology; GABA; Glutamate Decarboxylase - genetics; Glutamate Decarboxylase - physiology; GnRH; Gonadotropin-Releasing Hormone - metabolism; Mice; Mice, Knockout; Models, Biological; neuronal migration; Neurons - metabolism; Neurons - physiology; Nose - embryology; Nose - metabolism; Prosencephalon - embryology; Prosencephalon - metabolism; Vertebrates: endocrinology; Migration; Rodentia; Gonadotropin RH; Hypothalamic hormone; Vertebrata; Mammalia; Mouse; Animal; neuronal migration; Neurotransmitter; GABA; Mutation; Hormone releasing factor; GnRH
• ISSN: 0953-8194; 1365-2826
• DOI: 10.1111/j.1365-2826.2007.01623.x

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 γ‐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.