The hypothalamus-pituitary-gonadal (HPG) axis is the most critical modulator of reproductive function. Genetic or environmental insults to the HPG axis during developmental windows can persist into adulthood, and processes such as gonadal hormone synthesis, timing of puberty, and fertility can be affected. At the level of the hypothalamus, multiple regions develop at different times and are under the control of a concert of signaling pathways and transcription factors required for their patterning and maturation. In this review, we highlight factors and pathways involved in specification and ultimate differentiation of neuronal and other cellular subtypes of the hypothalamus contributing to the HPG axis. Specifically, we discuss development of the arcuate and anteroventral periventricular nuclei, as well as forebrain development as it relates to reproductive function. Precise control of kisspeptin and gonadotropin-releasing hormone neuron, as well as tanycyte, development is necessary for understanding and ultimately treating developmental disruptions resulting in infertility.
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