Fertility-regulating Kiss1 neurons arise from hypothalamic POMC-expressing progenitors

J Neurosci. 2015 Apr 8;35(14):5549-56. doi: 10.1523/JNEUROSCI.3614-14.2015.


Hypothalamic neuronal populations are central regulators of energy homeostasis and reproductive function. However, the ontogeny of these critical hypothalamic neuronal populations is largely unknown. We developed a novel approach to examine the developmental pathways that link specific subtypes of neurons by combining embryonic and adult ribosome-tagging strategies in mice. This new method shows that Pomc-expressing precursors not only differentiate into discrete neuronal populations that mediate energy balance (POMC and AgRP neurons), but also into neurons critical for puberty onset and the regulation of reproductive function (Kiss1 neurons). These results demonstrate a developmental link between nutrient-sensing and reproductive neuropeptide synthesizing neuronal populations and suggest a potential pathway that could link maternal nutrition to reproductive development in the offspring.

Keywords: gene expression; hypothalamus; metabolism; reproduction.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Agouti-Related Protein / genetics
  • Agouti-Related Protein / metabolism
  • Animals
  • Dependovirus / genetics
  • Embryo, Mammalian
  • Gene Expression Regulation, Developmental / genetics*
  • Genetic Vectors / physiology
  • Green Fluorescent Proteins / genetics
  • Green Fluorescent Proteins / metabolism
  • Hypothalamus / cytology*
  • Immunoprecipitation
  • Kisspeptins / genetics
  • Kisspeptins / metabolism*
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Microarray Analysis
  • Neurons / metabolism*
  • Pro-Opiomelanocortin / genetics
  • Pro-Opiomelanocortin / metabolism*
  • RNA, Messenger / metabolism
  • Stem Cells / physiology*
  • T-Box Domain Proteins / genetics
  • T-Box Domain Proteins / metabolism


  • Agouti-Related Protein
  • Agrp protein, mouse
  • Kiss1 protein, mouse
  • Kisspeptins
  • RNA, Messenger
  • T-Box Domain Proteins
  • Tbx3 protein, mouse
  • enhanced green fluorescent protein
  • Green Fluorescent Proteins
  • Pro-Opiomelanocortin