Normal migration of the gonadotrophin-releasing
hormone (
GnRH) neurones during early development, from the olfactory region to the hypothalamus, is crucial for reproductive development in all vertebrates. The establishment of the
GnRH system includes tangential migration of
GnRH perikarya as well as extension of
GnRH fibres to various areas of the central nervous system (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 system and the effects of
GnRH knockdown using a newly developed
GnRH3:EGFP transgenic zebrafish line. We found that
enhanced green fluorescent protein is specifically and robustly expressed in
GnRH3 neurones and fibres.
GnRH3 fibres in zebrafish began to extend as early as 26 h post-fertilisation and by 4-5 days post-fertilisation had developed into an extensive network reaching the optic tract, telencephalon, hypothalamus, midbrain tegmentum and hindbrain.
GnRH3 fibres also innervated the retina and projected into the trunk via the spinal cord.
GnRH3 perikarya were observed migrating along their own fibres from the olfactory region to the preoptic area (POA) via the terminal nerve
ganglion and the ventral telencephalon.
GnRH3 cells were also observed in the trigeminal ganglion. The establishment of the
GnRH3 fibre network was disrupted by
morpholino-modified
antisense oligonucleotides directed against
GnRH3 causing abnormal fibre development and pathfinding, as well as anomalous
GnRH3 perikarya localisation. These findings support the hypothesis that
GnRH3 neurones migrate from the olfactory region to the POA and caudal hypothalamus. Novel data regarding the early development of the
GnRH3 fibre network in the CNS and beyond are described. Moreover we show, in vivo, that
GnRH3 is an important factor regulating
GnRH3 fibre pathfinding and neurone localisation in an autocrine fashion.