Promoter transgenics reveal multiple gonadotropin-releasing hormone-I-expressing cell populations of different embryological origin in mouse brain

Gonadotropin-releasing hormone-1 (GnRH-1) is thought to be expressed by a s ingle, highly spatially restricted group of neurons, which originate in the olfactory placode and migrate through the nose into the medial septum and hypothalamus from where they control fertility. Transgenic mice bearing a 1 3.5 kb GnRH-1-lacZ reporter construct were derived and found to express hig h levels of P-galactosidase mRNA and protein within the septohypothalamic G nRH neurons in a correct temporal and spatial manner. Unexpectedly, low lev els of p-galactosidase were also present in three further populations of ce lls within the lateral septum, bed nucleus of the stria terminalis, and tec tum. Analysis of wild-type mice with three different GnRH-1 antibodies reve aled distinct and transient patterns of GnRH-1 peptide expression during de velopment in all three of these populations revealed by transgenics. The sy nthesis of GnRH by cells of the lateral septum was the most persistent and remained until the third postnatal week. Embryonic "small eye" Pax-6 null m ice, which fail to develop an olfactory placode, were also examined and sho wn to have equivalent populations of GnRH-1-immunoreactive cells in the lat eral septum, tectum, and bed nucleus of the stria terminalis but none of th e migrating cells that form the septohypothalamic GnRH population. These re sults prove that so-called "ectopic" expression in promoter transgenic line s can reflect authentic developmental patterns of gene expression. They fur ther provide the first demonstration in mammalian brain that multiple neuro nal populations of different embryological origin express GnRH-1 peptide du ring embryonic and postnatal development.