Gonadotropin-releasing hormone (GnRH) neurons (GnRH-ns) are hypothalamic neuroendocrine neurons controlling pubertal onset and fertility in most vertebrates by the strictly regulated release of the GnRH peptide that consists of pulses and surges. Even though GnRH-ns exert their physiological function in the hypothalamus, these unique neurons developmentally originate outside the brain, from stem cells located in the nasal placode. During embryogenesis the GnRH-ns migrate along the axons of the terminal nerve to arrive to the hypothalamus. Notably, GnRH-ns migration also relies on correct formation of the olfactory ensheathing cells (OECs), an olfactory system specific glial population that migrate with the GnRH-ns. After the migration of the GnRH-ns and in early postnatal life, GnRH-ns undergo alterations in their activity, biosynthetic profile and connectivity, including axon elongation to the median eminence and morphological remodeling of GnRH axons, critical for their network integration and synaptic communication with other neuronal populations.
Altogether, these developmental dynamics (during both embryonic development and early postnatal life) cooperate to the proper establishment of a functional GnRH neuronal system, therefore ensuring reproductive function. Indeed, defective GnRH neuron system formation and function represent the major cause of isolated GnRH deficiency, a genetically and phenotypically heterogenous group of disorders, characterized by absence of puberty and infertility. GnRH deficiency- phenotypic presentation can significantly vary in both sexes depending on the: (i) presence or absence of sense of smell (i.e. Kallmann syndrome); (ii) presence or absence of non-reproductive comorbidities, iii) GnRH secretory pattern defects and iv) timing of reproductive defects (i.e. Constitutional delay of growth and puberty).
Within the last 30 years, several molecular and cellular mechanisms underlying these complex and finely regulated biological processes have been elucidated; up to 50% of isolated GnRH deficiency causative genes have been identified, improving our understanding on the identity of the key cellular populations involved in the process of GnRH neuronal development. However, several aspects of GnRH neuron ontogenesis, as well as the mechanisms driving GnRH neuronal migration and maturation processes are still elusive, pointing towards the need to uncover novel causative genes and address several open questions.
In the present Research Topic, we wish to provide a comprehensive overview of the progresses made in the understanding of physiological and pathological GnRH neuron development. In particular, we seek to tackle not only unclear aspects of GnRH-ns physiology including, such as the definition of transcriptomic profiles throughout the development and the identification of axon guidance cues regulating neurite extension to the ME, but also novel and so far undescribed insights, as the role of extrahypothalamic GnRH-ns or the effects of environmental factors on GnRH-ns development.
We welcome original research papers and review articles that focus on, but are not limited to, the following topics:
- cellular and molecular mechanisms regulating GnRH-ns development and function;
- genetic determinants underlying inheritable forms of GnRH deficiency;
- new insights on environmental cues influencing GnRH-ns physiology.
Gonadotropin-releasing hormone (GnRH) neurons (GnRH-ns) are hypothalamic neuroendocrine neurons controlling pubertal onset and fertility in most vertebrates by the strictly regulated release of the GnRH peptide that consists of pulses and surges. Even though GnRH-ns exert their physiological function in the hypothalamus, these unique neurons developmentally originate outside the brain, from stem cells located in the nasal placode. During embryogenesis the GnRH-ns migrate along the axons of the terminal nerve to arrive to the hypothalamus. Notably, GnRH-ns migration also relies on correct formation of the olfactory ensheathing cells (OECs), an olfactory system specific glial population that migrate with the GnRH-ns. After the migration of the GnRH-ns and in early postnatal life, GnRH-ns undergo alterations in their activity, biosynthetic profile and connectivity, including axon elongation to the median eminence and morphological remodeling of GnRH axons, critical for their network integration and synaptic communication with other neuronal populations.
Altogether, these developmental dynamics (during both embryonic development and early postnatal life) cooperate to the proper establishment of a functional GnRH neuronal system, therefore ensuring reproductive function. Indeed, defective GnRH neuron system formation and function represent the major cause of isolated GnRH deficiency, a genetically and phenotypically heterogenous group of disorders, characterized by absence of puberty and infertility. GnRH deficiency- phenotypic presentation can significantly vary in both sexes depending on the: (i) presence or absence of sense of smell (i.e. Kallmann syndrome); (ii) presence or absence of non-reproductive comorbidities, iii) GnRH secretory pattern defects and iv) timing of reproductive defects (i.e. Constitutional delay of growth and puberty).
Within the last 30 years, several molecular and cellular mechanisms underlying these complex and finely regulated biological processes have been elucidated; up to 50% of isolated GnRH deficiency causative genes have been identified, improving our understanding on the identity of the key cellular populations involved in the process of GnRH neuronal development. However, several aspects of GnRH neuron ontogenesis, as well as the mechanisms driving GnRH neuronal migration and maturation processes are still elusive, pointing towards the need to uncover novel causative genes and address several open questions.
In the present Research Topic, we wish to provide a comprehensive overview of the progresses made in the understanding of physiological and pathological GnRH neuron development. In particular, we seek to tackle not only unclear aspects of GnRH-ns physiology including, such as the definition of transcriptomic profiles throughout the development and the identification of axon guidance cues regulating neurite extension to the ME, but also novel and so far undescribed insights, as the role of extrahypothalamic GnRH-ns or the effects of environmental factors on GnRH-ns development.
We welcome original research papers and review articles that focus on, but are not limited to, the following topics:
- cellular and molecular mechanisms regulating GnRH-ns development and function;
- genetic determinants underlying inheritable forms of GnRH deficiency;
- new insights on environmental cues influencing GnRH-ns physiology.