Early development of forebrain gonadotrophin-releasing hormone (GnRH) neurones and the role of GnRH as an autocrine migration factor.

Normal migration of the GnRH-I neurones during early development, from the olfactory region to the hypothalamus, is crucial for reproductive development in all vertebrates. The establishment of the GnRH-I system includes tangential migration of GnRH-I perikarya as well as extension of GnRH-I fibres to various areas of the CNS. The exact spatio-temporal nature of this process, as well as the factors governing it, are not fully understood. We studied the development of the GnRH-I system and the effects of GnRH-I knockdown using a newly developed GnRH-I:EGFP transgenic zebrafish line. We found that EGFP is specifically and robustly expressed in GnRH-I neurones and fibres. GnRH-I fibres in zebrafish began to extend as early as 26 hours post-fertilisation and by 4-5 days post-fertilisation (dpf) had developed into an extensive network reaching the optic tract, telencephalon, hypothalamus, midbrain tegmentum and hindbrain. GnRH-I fibres also innervated the retina and projected into the trunk via the spinal cord. GnRH-I perikarya were observed migrating along their own fibres from the olfactory region to the preoptic area (POA) via the terminal nerve ganglion (TNg) and the ventral telencephalon. GnRH-I cells were also observed in the trigeminal ganglion. The establishment of the GnRH-I fibre network was disrupted by morpholino-modified antisense oligonucleotides (MO) directed against GnRH-I causing abnormal fibre development and pathfinding, as well as anomalous GnRH-I perikarya localisation. These findings support the hypothesis that GnRH-I neurones migrate from the olfactory region to the POA and caudal hypothalamus. Novel data regarding the early development of the GnRH-I fibre network in the CNS and beyond is described. Moreover we show, in vivo, that GnRH-I is an important factor regulating GnRH-I fibre pathfinding and neurone localisation in an autocrine fashion.