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Embryological origins of GnRH Neurons

المؤلف:  Wass, J. A. H., Arlt, W., & Semple, R. K. (Eds.).

المصدر:  Oxford Textbook of Endocrinology and Diabetes

الجزء والصفحة:  3rd edition , p1250-1251

2026-10-14

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 During embryologic development, nascent GnRH neurons are first identified in the nasal (olfactory) placode. Initial GnRH cell migration toward the hypothalamus is guided by olfactory/ vomeronasal neuron axons projecting toward the olfactory bulb, with subsequent migration guided by neurons that project caudally into the forebrain (Figure 1). Once reaching the hypothalamus, GnRH cells extend processes to the median eminence and gain access to the hypophyseal portal system.

Fig1. Schematic of embryological GnRH cell migration from the nasal epithelium to the hypothalamus, guided by olfactory/ vomeronasal neurons. Adapted with permission from Stamou MI, Cox KH, Crowley WF, Jr. Discovering Genes Essential to the Hypothalamic Regulation of Human Reproduction Using a Human Disease Model: Adjusting to Life in the ‘- Omics’ Era. Endocr Rev 2015; 36:603– 21. (Ref 5) Copyright 2015 Oxford University Press.

As olfactory neurons form a pathway to guide GnRH neuronal migration, appropriate GnRH cell migration is dependent on normal olfactory system development. This is exemplified by Kallmann syndrome, in which abnormal olfactory system development renders an inadequate guidance infrastructure for GnRH neurons. Accordingly, individuals with Kallmann syndrome have congenital hypogonadotropic hypogonadism in addition to anosmia (absent sense of smell). Kallmann syndrome was first described in patients with deletion of the ANOS1 (formerly KAL1) gene, which encodes a matrix glycoprotein important for fetal olfactory development. Human fetuses with X- linked Kallmann syndrome exhibit arrested migration of GnRH- immunoreactive cells along terminal nerve fascicles in the nasal mucosa or at the cribriform plate. Numerous other genes related to fetal GnRH cell migration underlie forms of congenital hypogonadotropic hypogonadism with and without anosmia.