THE GONADOTROPIN-RELEASING-HORMONE SYSTEM DOES NOT DEVELOP IN SMALL-EYE (SEY) MOUSE PHENOTYPE

This study examined the development of the gonadotropin releasing-horm one (GnRH) system in a spontaneous mouse mutation, Small-Eye (Sey). Th is phenotype is due to a point mutation in the developmental control g ene Pax-6 and results in failed development of the eye and olfactory p lacodes in homozygous (Sey/Sey) embryos and a variety of eye abnormali ties in heterozygotes (Sey/+). Therefore, Sey/Sey embryos provided a n aturally occurring olfactory placode ablation to ask whether all of th e GnRH neurons found in the adult mouse forebrain arise from the olfac tory epithelium. In Sey/Sey embryos, GnRH-immunoreactive neurons were not present in either the presumptive nasal regions or in any area of the brain at any embryonic age. In contrast, in Sey/+ embryos, there w as no apparent effect on either GnRH cell proliferation or migration. These data support and extend the hypothesis that GnRH neurons in mice originate in the olfactory placodes and also demonstrate that two nor mal alleles of Pax-6 are not required for GnRH system development. (C) 1998 Elsevier Science B.V.