title: Zebrafish adult-derived hypothalamic neurospheres generate gonadotropin-releasing hormone (GnRH) neurons.
abstract: Gonadotropin-releasing hormone (GnRH) is a hypothalamic decapeptide essential for fertility in vertebrates. Human male patients lacking GnRH and treated with hormone therapy can remain fertile after cessation of treatment suggesting that new GnRH neurons can be generated during adult life. We used zebrafish to investigate the neurogenic potential of the adult hypothalamus. Previously we have characterized the development of GnRH cells in the zebrafish linking genetic pathways to the differentiation of neuromodulatory and endocrine GnRH cells in specific regions of the brain. Here, we developed a new method to obtain neural progenitors from the adult hypothalamus in vitro. Using this system, we show that neurospheres derived from the adult hypothalamus can be maintained in culture and subsequently differentiate glia and neurons. Importantly, the adult derived progenitors differentiate into neurons containing GnRH and the number of cells is increased through exposure to either testosterone or GnRH, hormones used in therapeutic treatment in humans. Finally, we show in vivo that a neurogenic niche in the hypothalamus contains GnRH positive neurons. Thus, we demonstrated for the first time that neurospheres can be derived from the hypothalamus of the adult zebrafish and that these neural progenitors are capable of producing GnRH containing neurons.
authors.affiliation: Centro Interdisciplinario de Neurociencia de Valparaíso (CINV), Facultad de Ciencias, Universidad de Valparaíso, Pasaje Harrington 269, Valparaíso 2340000, Chile Whitehead Institute for Biomedical Research (WIBR), 9 Cambridge Center, Cambridge, MA 02142, USA.
authors.forename: Christian
authors.initials: C
authors.lastname: Cortés-Campos
authors.affiliation: Centro Interdisciplinario de Neurociencia de Valparaíso (CINV), Facultad de Ciencias, Universidad de Valparaíso, Pasaje Harrington 269, Valparaíso 2340000, Chile Centro Andaluz de Biología del Desarrollo, Universidad Pablo de Olavide, Carretera de Utera km 1, Sevilla 41013, España.
authors.forename: Joaquín
authors.initials: J
authors.lastname: Letelier
authors.affiliation: Centro Interdisciplinario de Neurociencia de Valparaíso (CINV), Facultad de Ciencias, Universidad de Valparaíso, Pasaje Harrington 269, Valparaíso 2340000, Chile.
authors.forename: Ricardo
authors.initials: R
authors.lastname: Ceriani
authors.affiliation: Centro Interdisciplinario de Neurociencia de Valparaíso (CINV), Facultad de Ciencias, Universidad de Valparaíso, Pasaje Harrington 269, Valparaíso 2340000, Chile kathleen.whitlock@uv.cl.
authors.forename: Kathleen E
authors.initials: KE
authors.lastname: Whitlock
keywords: GnRH receptors; Kallmann syndrome; Testosterone