Regulation of gonadotropin-releasing hormone (GnRH) gene expression duringGnRH neuron migration in the mouse

The mechanisms underlying the mig ration of the gonadotropin-releasing horm one (GnRH) neurons from the nose into the forebrain are not resolved. In an attempt to characterize further the migrating GnRH neurons, we have employ ed in situ hybridization techniques and transgenic mouse models to examine levels of GnRH mRNA and GnRH gene transcription in GnRH neurons during migr ation in the mouse. In the first experiment, cellular levels of GnRH mRNA i n neurons located throughout the nose and forebrain were examined in embryo nic 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 forebra in (p < 0.05) was found to increase significantly from E12.5 to E19.5 and f rom E24.5 to E19.5, respectively. However, cellular levels of GnRH mRNA wer e not significantly different in neurons located in the nose compared with the brain at each developmental age. In the second experiment, levels of Gn RH gene transcription were investigated at E14.5 using two different GNLZ t ransgenic mouse lines in which 13.5 kb of GnRH gene sequences direct the ex pression of the LacZ reporter to the nucleus of GnRH neurons. Migrating GnR H neurons displayed up to a 3-fold increase (p < 0.01) in transgene express ion, an index of GnRH transcription, precisely as they approached and enter ed the forebrain. These results indicate that GnRH gene expression in migra ting GnRH neurons is likely regulated by temporal as well as spatial factor s and that, as found postnatally, this may involve both transcriptional and post-transcriptional regulatory mechanisms. Copyright <(c)> 2001 S. Karger AG, Basel.