F1000Prime Recommendation of [Hu Y et al., Endocrinology 2013, 154(1):388-99].

This paper by Hu and coworkers describes the role of phosphoinositide 3-kinase (PI3K) as the main intracellular pathway activated by fibroblast growth factor receptor 1 (FGFR1) in the migration of GnRH neurons, and neurite elongation of olfactory bulb neurons, in chick olfactory placode explants. Moreover, a similar role in gonadotropin-releasing hormone (GnRH) neuronal migration is also observed in chick embryo and human embryonic neuroblasts. More than 40 heterozygous FGFR1 mutations have been described that account for roughly 10% of cases of autosomal Kallmann's syndrome, a disorder associated with infertility, due to variable GnRH deficiency, and anosmia and, sometimes, other non-reproductive clinical features. The chick embryo provides an excellent model system for studying the development of higher vertebrates, wherein growth accompanies morphogenesis, and the recent demonstration {1} that also in the chick, GnRH-1 neurons originate in the olfactory placode makes this animal model very suitable for the study of the mechanisms involved in the migration of GnRH neurons. It is thanks to this experimental model, which allows the pharmacological manipulation of the embryo 'in ovo', that the authors demonstrate the main role of PI3K p110alpha isoform as a downstream effector of FGFR1 signaling for GnRH neuronal migration. Actually, these results (even if limited at the bird model) together with, as suggested by the authors, the possible sharing of this intracellular pathway by some of the other several factors involved in the disease might provide useful information to unveil some molecular aspects of the pathogenesis of Kallmann's syndrome. References 1. Specification of GnRH-1 neurons by antagonistic FGF and retinoic acid signaling. Sabado V, Barraud P, Baker CV, Streit A. Dev Biol 2012 Feb 15; 362(2):254-62 PMID: 22200593 DOI: 10.1016/j.ydbio.2011.12.016