MIGRATION OF THE LHRH NEURONS FROM THE NASAL REGION TO THE FOREBRAIN.

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In the chick embryo, LHRH neurons originate in the olfactory placode and migrate to the forebrain during embryonic days(E) 3.5-11. Examination of the normal development of LHRH neurons indicates that two major pathways of LHRH neuron migration exist in the brain. The main pathway of LHRH neuron migration largely corresponds to the course of the olfactory related fibers. At the most caudal level of this pathway, where the septal area develops, many LHRH neurons turn ventrally in direction of the ventral preoptic area. These LHRH neurons deviate from the olfactory related fibers. The dispersion of LHRH neurons from the nerve fibers implicates that another guidance cues contribute to the migration of LHRH neurons towards the preoptic area. From these findings, it is proposed that a character of LHRH neurons in the preoptic area differs from that in the septal area.To examine whether the birthdate of LHRH neurons influences their final locations, a single dose of BrdU was injected into eggs at different stages. LHRH neurons born at E2.5-4.5 were found in the entire final distribution areas at E11.5 and E18.5. In contrast, LHRH neurons born at E5.5-6.5 were not observed in the ventral preoptic region. It might be possible that late-generated LHRH neurons could not move in direction to the preoptic area. Structural and chemical guidance substrates for LHRH neuron migration might be lost at that time when late-generated LHRH neurons migrate toward the preoptic area.Netrin-1 is a diffusible molecule that guides various axons and cells migration. Netrin-1 mRNA was strongly expressed in the ventral hypothalamus but not in the dorsomedial forebrain at E7.5. Netrin-1 may be a candidate molecule for LHRH neuron migration from the dorsal preseptal area to the ventral preoptic area.