956 Experientia 46 (1990), Birkh/iuser Verlag, CH-4010 Basel/Switzerland Reviews The migration of luteinizing hormone-releasing hormone (LHRH) neurons from the medial olfactory placode into the medial basal forebrain M. Schwanzel.Fukuda and D. W. Pfaff The Rockefeller University, Laboratory of Neurobiology and Behavior, 1230 York Avenue, New York (New York 10021, USA) Summary. Over the years, investigators have noticed, in a wide variety of species of vertebrates, large numbers of cells migrating from the olfactory placode to the forebrain. These cells were considered to be Schwann cells or ganglion cells of the terminalis nerve. Recently, immunocytochemical localization studies have shown that many of these migrating cells contain luteinizing hormone-releasing hormone (LHRH), a brain peptide that regulates reproductive functions by evoking the release of luteinizing hormone and follicle-stimulating hormone from the anterior pituitary gland. The origin of LHRH cells in the epithelium of the medial olfactory placode, their migration across the nasal septum and into the forebrain, with branches of the terminalis nerve, also a derivative of the medial part of the olfactory placode, has led to some interesting speculations, from evolutionary and physiological perspectives, about the origin of these cells and the role of the terminalis nerve in their migration. Key words. Terminalis nerve; olfactory pit; nasal placode. Development of the olfactory placodes In most vertebrates, the olfactory placodes appear about midway in gestation as thickenings of the ectoderm on the ventrolateral sides of the head. Within a day, the thickened epithelia of the olfactory placodes invaginate to form the olfactory pits, and soon after a secondary recess, the anlage of the vomeronasal organ, forms in the medial wall of either olfactory pit. The right and left olfactory pits are separated from each other by the devel- oping nasal septum. The terminalis and vomeronasal nerves arise from the medial part of either olfactory pit and the olfactory nerves arise from the dorsal regions of the pit, just lateral to the anlage of the vomeronasal organ. The central processes of the olfactory nerves grow toward the forebrain and terminate in the main olfactory bulb. The central processes of the vomeronasal nerves also grow toward the forebrain but these axons end in the accessory olfactory bulb, found on the dorsocaudal as- pect of either main olfactory bulb. The terminali s nerves, in contrast to the olfactory and vomeronasal nerves, are accompanied by clusters of ganglion cells as they cross the nasal septum and enter the mediobasal forebrain in company with branches of the anterior cerebral artery. The central processes of the terminalis nerves have been traced into the medial septal and the medial preoptic nuclei 22, 23, 25 General phenomenon of cell migration from the olfactory placode The migration of large numbers of cells from the olfacto- ry placode during development has been observed in a wide variety of species of vertebrates including mice 9; rats~l,24; frogs21; turtlesZZ; porpoise33; whalesT; swine z; chickens 27, as, 55 and humans 3, 34, 36, 3v. At least two types of cells have been described in migration from the epithelium of the olfactory placode 9.11, z4, 2v, s4, one of which is considered to be a progenitor of the Schwann cells which accompany fascicles of the olfactory nerves, and the other ganglion cells of the terminalis nerve. Pear- son, in his studies of the development of the olfactory 37 and terminalis nerves 36 in human fetuses, traced the mi- gration of cells fi'om the medial part of the olfactory placode along fibers of the terminalis and vomeronasal nerves into the ganglion terminale 23. This is the major ganglion of the terminalis nerve and it is found medial to the olfactory nerves on the cribriform plate of the eth- moid bone. Pearson noted that the external limiting membrane of the brain had disappeared at the point of contact between the ganglion terminale and the fore- brain, and that fibers of the terminalis nerve continued into the forebrain. He interpreted the continuous stream of cells that accompanied these fibers as a 'migration of ceils from the brain out into the ganglion', and he sug- gested that the terminalis nerve develops from sensory components derived from the olfactory placode and au- tonomic components derived from the forebrain. Influence of olfactory placode-derived elements on differentiation of the forebrain The influence of the olfactory nerves on development of the olfactory bulb and forebrain was observed in experi- mental studies in Amblystoma, in which removal of the nasal placode or pit resulted in an absence of the olfacto- ry bulb and a reduction in size of the forebrain 8. These data were extrapolated to human arhinencephalic fetus- es ~6, in which the arhinencephaly was postulated to be the result of defective development of the olfactory pla- code. The strongest evidence in support of this postulate came from the experimental studies of Graziadei and co-workers in mammals ~2, 13 and in amphibians 26's3. These investigators showed conclusively that elements of the embryonic olfactory placode affect the organization of the forebrain 6.