Regulation of Gonadotropin-Releasing Hormone (GnRH) Gene Expression during GnRH Neuron Migration in the Mouse

Abstract

The mechanisms underlying the migration of the gonadotropin-releasing hormone (GnRH) neurons from the nose into the forebrain are not resolved. In an attempt to characterize further the migrating GnRH neurons, we have employed in situ hybridization techniques and transgenic mouse models to examine levels of GnRH mRNA and GnRH gene transcription in GnRH neurons during migration in the mouse. In the first experiment, cellular levels of GnRH mRNA in neurons located throughout the nose and forebrain were examined in embryonic day (E) 12.5, 14.5, 16.5 and 19.5 mice using in situ hybridization. The GnRH mRNA content of cells located in both the nose (p < 0.01) and forebrain (p < 0.05) was found to increase significantly from E12.5 to E19.5 and from E14.5 to E19.5, respectively. However, cellular levels of GnRH mRNA were not significantly different in neurons located in the nose compared with the brain at each developmental age. In the second experiment, levels of GnRH gene transcription were investigated at E14.5 using two different GNLZ transgenic mouse lines in which 13.5 kb of GnRH gene sequences direct the expression of the LacZ reporter to the nucleus of GnRH neurons. Migrating GnRH neurons displayed up to a 3-fold increase (p < 0.01) in transgene expression, an index of GnRH transcription, precisely as they approached and entered the forebrain. These results indicate that GnRH gene expression in migrating GnRH neurons is likely regulated by temporal as well as spatial factors and that, as found postnatally, this may involve both transcriptional and post-transcriptional regulatory mechanisms.