title: Fgf10-expressing tanycytes add new neurons to the appetite/energy-balance regulating centers of the postnatal and adult hypothalamus.
abstract: Increasing evidence suggests that neurogenesis occurs in the postnatal and adult mammalian hypothalamus. However, the identity and location of the putative progenitor cells is under much debate, and little is known about the dynamics of neurogenesis in unchallenged brain. Previously, we postulated that Fibroblast growth factor 10-expressing (Fgf10(+)) tanycytes constitute a population of progenitor cells in the mouse hypothalamus. Here, we show that Fgf10(+) tanycytes express markers of neural stem/progenitor cells, divide late into postnatal life, and can generate both neurons and astrocytes in vivo. Stage-specific lineage-tracing of Fgf10(+) tanycytes using Fgf10-creERT2 mice, reveals robust neurogenesis at postnatal day 28 (P28), lasting as late as P60. Furthermore, we present evidence for amplification of Fgf10-lineage traced neural cells within the hypothalamic parenchyma itself. The neuronal descendants of Fgf10(+) tanycytes predominantly populate the arcuate nucleus, a subset of which express the orexigenic neuronal marker, Neuropeptide-Y, and respond to fasting and leptin-induced signaling. These studies provide direct evidence in support of hypothalamic neurogenesis during late postnatal and adult life, and identify Fgf10(+) tanycytes as a source of parenchymal neurons with putative roles in appetite and energy balance.
authors.affiliation: School of Biological Sciences, University of East Anglia, Norwich, NR4 7TJ, United Kingdom.
authors.forename: Niels
authors.initials: N
authors.lastname: Haan
authors.forename: Timothy
authors.initials: T
authors.lastname: Goodman
authors.forename: Alaleh
authors.initials: A
authors.lastname: Najdi-Samiei
authors.forename: Christina M
authors.initials: CM
authors.lastname: Stratford
authors.forename: Ritva
authors.initials: R
authors.lastname: Rice
authors.forename: Elie
authors.initials: E
authors.lastname: El Agha
authors.forename: Saverio
authors.initials: S
authors.lastname: Bellusci
authors.forename: Mohammad K
authors.initials: MK
authors.lastname: Hajihosseini
mesh_terms: D000367:Age Factors; D000704:Analysis of Variance; D000818:Animals; D000831:Animals, Newborn; D001066:Appetite / Q000187:drug effects / Q000502:physiology*; D001426:Bacterial Proteins / Q000235:genetics; D001973:Bromodeoxyuridine; D003600:Cytosol / Q000378:metabolism*; D004734:Energy Metabolism / Q000187:drug effects / Q000502:physiology*; D004965:Estrogen Antagonists / Q000494:pharmacology; D000071438:Fatty Acid-Binding Protein 7; D050556:Fatty Acid-Binding Proteins / Q000378:metabolism; D051526:Fibroblast Growth Factor 10 / Q000235:genetics / Q000378:metabolism*; D005508:Food Deprivation / Q000502:physiology; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects / Q000235:genetics; D007031:Hypothalamus / Q000187:drug effects / Q000254:growth & development / Q000378:metabolism*; D008164:Luminescent Proteins / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D009419:Nerve Tissue Proteins / Q000378:metabolism; D055495:Neurogenesis / Q000187:drug effects / Q000502:physiology*; D010671:Phenylurea Compounds / Q000008:administration & dosage; D011506:Proteins / Q000235:genetics; D022661:RNA, Untranslated; D013629:Tamoxifen / Q000494:pharmacology; D001616:beta-Galactosidase / Q000378:metabolism
chemical_list: D001426:Bacterial Proteins; D004965:Estrogen Antagonists; C086936:Fabp7 protein, mouse; D000071438:Fatty Acid-Binding Protein 7; D050556:Fatty Acid-Binding Proteins; C496464:Fgf10 protein, mouse; D051526:Fibroblast Growth Factor 10; C110853:Gt(ROSA)26Sor non-coding RNA, mouse; D008164:Luminescent Proteins; D009419:Nerve Tissue Proteins; D010671:Phenylurea Compounds; D011506:Proteins; D022661:RNA, Untranslated; C413663:fluorescent protein 583; C054562:yellow fluorescent protein, Bacteria; D013629:Tamoxifen; C032766:ethylene diurea; D001616:beta-Galactosidase; D001973:Bromodeoxyuridine
references.citation: J Biol Chem. 2006 Jun 9;281(23):15694-700
references.pmid: 16597617
references.citation: Development. 2006 Apr;133(7):1359-66
references.pmid: 16510502
references.citation: J Neurosci. 2010 Jan 13;30(2):723-30
references.pmid: 20071537
references.citation: Z Zellforsch Mikrosk Anat. 1971;121(1):1-13
references.pmid: 5112429
references.citation: J Comp Neurol. 2001 Apr 23;433(1):101-14
references.pmid: 11283952
references.citation: Curr Opin Neurobiol. 2012 Oct;22(5):737-46
references.pmid: 22554882
references.citation: J Neurosci. 2001 Sep 1;21(17):6706-17
references.pmid: 11517260
references.citation: Genes Dev. 1998 Oct 15;12(20):3156-61
references.pmid: 9784490
references.citation: Mol Cell Neurosci. 2009 Jul;41(3):337-47
references.pmid: 19409493
references.citation: PLoS One. 2012;7(6):e38452
references.pmid: 22719891
references.citation: J Biochem. 2011 Feb;149(2):121-30
references.pmid: 20940169
references.citation: Science. 2011 Nov 25;334(6059):1133-7
references.pmid: 22116886
references.citation: Development. 2010 Oct;137(20):3439-48
references.pmid: 20843859
references.citation: Glia. 2006 Jul;54(1):21-34
references.pmid: 16652340
references.citation: Science. 2005 Oct 28;310(5748):683-5
references.pmid: 16254186
references.citation: Biochem Biophys Res Commun. 2005 Dec 16;338(2):1248-55
references.pmid: 16263090
references.citation: Nat Rev Neurosci. 2007 Jun;8(6):481-8
references.pmid: 17514200
references.citation: J Comp Neurol. 2008 May 1;508(1):28-44
references.pmid: 18288691
references.citation: Dev Biol. 2007 Mar 1;303(1):295-310
references.pmid: 17196193
references.citation: Neuron. 2009 Jul 16;63(1):48-62
references.pmid: 19607792
references.citation: Nat Cell Biol. 2012 Oct;14(10):999-1012
references.pmid: 22940906
references.citation: J Comp Neurol. 2007 Nov 10;505(2):209-20
references.pmid: 17853440
references.citation: Behav Brain Res. 2010 May 1;209(1):1-12
references.pmid: 20035790
references.citation: Neuron. 2011 May 26;70(4):687-702
references.pmid: 21609825
references.citation: Science. 2005 Oct 28;310(5748):679-83
references.pmid: 16254185
references.citation: Eur J Neurosci. 2010 Dec;32(12):2042-52
references.pmid: 21143659
references.citation: Nature. 2010 Jun 10;465(7299):783-7
references.pmid: 20505669
references.citation: Am J Physiol Regul Integr Comp Physiol. 2010 Aug;299(2):R632-41
references.pmid: 20538900
references.citation: Dev Dyn. 2009 Feb;238(2):376-85
references.pmid: 18773495
references.citation: J Clin Invest. 2012 Jan;122(1):142-52
references.pmid: 22201680
references.citation: Mol Cell Neurosci. 2008 Apr;37(4):857-68
references.pmid: 18329286
references.citation: Curr Opin Neurobiol. 2012 Oct;22(5):754-61
references.pmid: 22503352
references.citation: J Neurosci. 2004 Mar 24;24(12):2886-97
references.pmid: 15044527
references.citation: Cell. 2008 Feb 22;132(4):645-60
references.pmid: 18295581
references.citation: Exp Neurol. 2005 Apr;192(2):251-64
references.pmid: 15755543
references.citation: J Neurosci. 2011 Mar 30;31(13):5055-66
references.pmid: 21451043
references.citation: Development. 2000 Feb;127(3):483-92
references.pmid: 10631169
references.citation: Exp Neurol. 1973 Oct;41(1):163-73
references.pmid: 4743483
references.citation: Development. 2005 May;132(9):2157-66
references.pmid: 15800000
references.citation: Eur J Neurosci. 2010 May;31(9):1533-48
references.pmid: 20525067
references.citation: Int Rev Cytol. 2005;247:89-164
references.pmid: 16344112
references.citation: Nat Neurosci. 2012 Mar 25;15(5):700-2
references.pmid: 22446882
references.citation: J Neurosci. 2004 Oct 6;24(40):8711-9
references.pmid: 15470137
references.citation: Front Oral Biol. 2008;12:160-177
references.pmid: 18391500
references.citation: Dev Cell. 2001 Sep;1(3):435-40
references.pmid: 11702954