Reelin provides an inhibitory signal in the migration of gonadotropin-releasing hormone neurons.
Gonadotropin-releasing hormone (GnRH) neurons, a small number of cells scattered in the hypothalamic region of the basal forebrain, play an important role in reproductive function. These cells originate in the olfactory placode and migrate into the basal forebrain in late embryonic life. Here, we show that reelin, which is expressed along the route of the migrating cells, has an inhibitory role in guiding GnRH neurons to the basal forebrain. Only a small (approximately 5%) subpopulation of these neurons expresses one of the reelin receptors (ApoER2/Lrp8), and all GnRH neurons appear to lack the intracellular adaptor protein Dab1, suggesting that the function of reelin is not mediated by the conventional signal transduction pathway. The importance of reelin in the establishment of GnRH neurons in the hypothalamus was confirmed by our finding that the brains of developing and adult reeler mice of both sexes contained a markedly reduced number of these neuroendocrine neurons. Furthermore, the testes of adult males showed dilation of seminiferous tubules and reduction in their density when compared with controls. Mutants lacking the reelin receptors ApoER2 and Vldlr, and scrambler mice lacking Dab1, showed a normal complement of GnRH neurons in the hypothalamus, confirming that the effect of reelin in their migration is independent of Dab1.
Cariboni
Anna
A
Department of Anatomy and Developmental Biology, University College London, London WC1E 6BT, UK.
Rakic
Sonja
S
Liapi
Anastasia
A
Maggi
Roberto
R
Goffinet
Andre
A
Parnavelas
John G
JG
D000818:Animals; D015816:Cell Adhesion Molecules, Neuronal / Q000502:physiology*; D002465:Cell Movement; D016326:Extracellular Matrix Proteins / Q000502:physiology*; D005260:Female; D007987:Gonadotropin-Releasing Hormone; D007031:Hypothalamus / Q000166:cytology; D026502:LDL-Receptor Related Proteins; D008297:Male; D051379:Mice; D008817:Mice, Mutant Strains; D009419:Nerve Tissue Proteins / Q000172:deficiency / Q000502:physiology*; D009474:Neurons / Q000737:chemistry* / Q000502:physiology*; D011247:Pregnancy; D016548:Prosencephalon / Q000166:cytology; D051381:Rats; D017207:Rats, Sprague-Dawley; D011973:Receptors, LDL / Q000172:deficiency / Q000502:physiology; D018110:Receptors, Lipoprotein / Q000172:deficiency / Q000502:physiology; D000091042:Reelin Protein; D012671:Seminiferous Tubules / Q000473:pathology; D012697:Serine Endopeptidases / Q000502:physiology*
D015816:Cell Adhesion Molecules, Neuronal; C103773:Dab1 protein, mouse; D016326:Extracellular Matrix Proteins; D026502:LDL-Receptor Related Proteins; D009419:Nerve Tissue Proteins; D011973:Receptors, LDL; D018110:Receptors, Lipoprotein; D000091042:Reelin Protein; C000717129:Reln protein, rat; C036053:VLDL receptor; C098773:low density lipoprotein receptor-related protein 8; D007987:Gonadotropin-Releasing Hormone; C000717128:Reln protein, mouse; D012697:Serine Endopeptidases