title: Fertility-regulating Kiss1 neurons arise from hypothalamic POMC-expressing progenitors.
abstract: 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.
authors: Department of Pharmacology, Center for Integrative Brain Research and Center for Developmental Therapeutics, Seattle Children's Research Institute, Seattle, Washington 98101.
authors: Elisenda
authors: http://orcid.org/0000-0002-7932-8556
authors: E
authors: Sanz
authors: Department of Biochemistry, Howard Hughes Medical Institute, Center for Integrative Brain Research and Center for Developmental Therapeutics, Seattle Children's Research Institute, Seattle, Washington 98101.
authors: Albert
authors: http://orcid.org/0000-0003-1674-7160
authors: A
authors: Quintana
authors: Department of Pharmacology.
authors: Jennifer D
authors: http://orcid.org/0000-0002-8865-5145
authors: JD
authors: Deem
authors: Department of Obstetrics and Gynecology, and Department of Physiology and Biophysics, University of Washington, Seattle, Washington 98195, and.
authors: Robert A
authors: http://orcid.org/0000-0002-5832-6412
authors: RA
authors: Steiner
authors: Department of Biochemistry, Howard Hughes Medical Institute.
authors: Richard D
authors: http://orcid.org/0000-0001-6587-0582
authors: RD
authors: Palmiter
authors: Department of Pharmacology, mcknight@u.washington.edu.
authors: G Stanley
authors: http://orcid.org/0000-0001-9531-2936
authors: GS
authors: McKnight
mesh_terms: D054369:Agouti-Related Protein / Q000235:genetics / Q000378:metabolism; D000818:Animals; D000229:Dependovirus / Q000235:genetics; D004622:Embryo, Mammalian; D018507:Gene Expression Regulation, Developmental / Q000235:genetics*; D005822:Genetic Vectors / Q000502:physiology; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D007031:Hypothalamus / Q000166:cytology*; D047468:Immunoprecipitation; D059648:Kisspeptins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D046228:Microarray Analysis; D009474:Neurons / Q000378:metabolism*; D011333:Pro-Opiomelanocortin / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D013234:Stem Cells / Q000502:physiology*; D020825:T-Box Domain Proteins / Q000235:genetics / Q000378:metabolism
chemical_list: D054369:Agouti-Related Protein; C515199:Agrp protein, mouse; C491407:Kiss1 protein, mouse; D059648:Kisspeptins; D012333:RNA, Messenger; D020825:T-Box Domain Proteins; C491460:Tbx3 protein, mouse; C485184:enhanced green fluorescent protein; D049452:Green Fluorescent Proteins; D011333:Pro-Opiomelanocortin
keywords: gene expression; hypothalamus; metabolism; reproduction