Cell and Tissue Research

, Volume 375, Issue 1, pp 23–39 | Cite as

Development of neuroendocrine neurons in the mammalian hypothalamus

  • Gonzalo Alvarez-BoladoEmail author


The neuroendocrine system consists of a heterogeneous collection of (mostly) neuropeptidergic neurons found in four hypothalamic nuclei and sharing the ability to secrete neurohormones (all of them neuropeptides except dopamine) into the bloodstream. There are, however, abundant hypothalamic non-neuroendocrine neuropeptidergic neurons developing in parallel with the neuroendocrine system, so that both cannot be entirely disentangled. This heterogeneity results from the workings of a network of transcription factors many of which are already known. Olig2 and Fezf2 expressed in the progenitors, acting through mantle-expressed Otp and Sim1, Sim2 and Pou3f2 (Brn2), regulate production of magnocellular and anterior parvocellular neurons. Nkx2-1, Rax, Ascl1, Neurog3 and Dbx1 expressed in the progenitors, acting through mantle-expressed Isl1, Dlx1, Gsx1, Bsx, Hmx2/3, Ikzf1, Nr5a2 (LH-1) and Nr5a1 (SF-1) are responsible for tuberal parvocellular (arcuate nucleus) and other neuropeptidergic neurons. The existence of multiple progenitor domains whose progeny undergoes intricate tangential migrations as one source of complexity in the neuropeptidergic hypothalamus is the focus of much attention. How neurosecretory cells target axons to the medial eminence and posterior hypophysis is gradually becoming clear and exciting progress has been made on the mechanisms underlying neurovascular interface formation. While rat neuroanatomy and targeted mutations in mice have yielded fundamental knowledge about the neuroendocrine system in mammals, experiments on chick and zebrafish are providing key information about cellular and molecular mechanisms. Looking forward, data from every source will be necessary to unravel the ways in which the environment affects neuroendocrine development with consequences for adult health and disease.


Arcuate nucleus Genomic regulatory networks Hypophysis Magnocellular Neurosecretory Paraventricular Parvocellular Periventricular nucleus Progenitor domain Supraoptic nucleus 



third ventricle


anterior commissure


agouti related neuropeptide


anterior hypothalamic area


anterior region of the hypothalamus


nucleus arcuatus of the hypothalamus


arginine vasopressin


CART (cocaine- and amphetamine-regulated transcript protein) prepropeptide


central nervous system


corticotropin releasing hormone


dorsomedial nucleus of the hypothalamus


growth hormone releasing hormone


gonadotropin releasing hormone


genomic regulatory network




kisspeptin (KiSS-1 metastasis-suppressor)


lateral hypothalamic area


mamillary region of the hypothalamus


mamillary body


melanin-concentrating hormone


median eminence


alpha-melanocyte-stimulating hormone


neuroendocrine (neurosecretory)


non-neuroendocrine (non-neurosecretory)


neuropeptide Y




premamillary area


preoptic region of the hypothalamus




periventricular nucleus


paraventricular nucleus of the hypothalamus


suprachiasmatic nucleus


supraoptic nucleus




tyrosine hydroxylase


thyrotropin releasing hormone


tuberal region of the hypothalamus


transcription factor


ventromedial nucleus of the hypothalamus


ventricular zone


zona limitans intrathalamica


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© Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Department Neuroanatomy, Institute of Anatomy and Cell BiologyUniversity of HeidelbergHeidelbergGermany

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