title: A distinctive layering pattern of mouse dentate granule cells is generated by developmental and adult neurogenesis.
abstract: New neurons are continuously added throughout life to the dentate gyrus of the mammalian hippocampus. During embryonic and early postnatal development, the dentate gyrus is formed in an outside-in layering pattern that may extend through adulthood. In this work, we sought to quantify systematically the relative position of dentate granule cells generated at different ages. We used 5'-bromo-2'-deoxyuridine (BrdU) and retroviral methodologies to birth date cells born in the embryonic, early postnatal, and adult hippocampus and assessed their final position in the adult mouse granule cell layer. We also quantified both developmental and adult-born cohorts of neural progenitor cells that contribute to the pool of adult progenitor cells. Our data confirm that the outside-in layering of the dentate gyrus continues through adulthood and that early-born cells constitute most of the adult dentate gyrus. We also found that substantial numbers of the dividing cells in the adult dentate gyrus were derived from early-dividing cells and retained BrdU, suggesting that a subpopulation of hippocampal progenitors divides infrequently from early development onward.
authors.affiliation: Laboratory of Genetics, The Salk Institute for Biological Studies, La Jolla, California 92037, USA.
authors.forename: Emily A
authors.initials: EA
authors.lastname: Mathews
authors.forename: Nicolás A
authors.initials: NA
authors.lastname: Morgenstern
authors.forename: Verónica C
authors.initials: VC
authors.lastname: Piatti
authors.forename: Chunmei
authors.initials: C
authors.lastname: Zhao
authors.forename: Sebastian
authors.initials: S
authors.lastname: Jessberger
authors.forename: Alejandro F
authors.initials: AF
authors.lastname: Schinder
authors.forename: Fred H
authors.initials: FH
authors.lastname: Gage
mesh_terms: D000367:Age Factors; D000818:Animals; D000831:Animals, Newborn; D001973:Bromodeoxyuridine / Q000378:metabolism; D002454:Cell Differentiation / Q000502:physiology; D049109:Cell Proliferation; D018891:Dentate Gyrus / Q000166:cytology / Q000196:embryology / Q000254:growth & development; D004622:Embryo, Mammalian; D005260:Female; D018507:Gene Expression Regulation, Developmental / Q000235:genetics / Q000502:physiology*; D049452:Green Fluorescent Proteins / Q000235:genetics; D019394:Ki-67 Antigen / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D055495:Neurogenesis / Q000235:genetics / Q000502:physiology*; D009474:Neurons / Q000502:physiology*; D010751:Phosphopyruvate Hydratase / Q000378:metabolism; D011247:Pregnancy; D055748:SOXB1 Transcription Factors / Q000235:genetics / Q000378:metabolism; D013234:Stem Cells / Q000502:physiology*
chemical_list: D019394:Ki-67 Antigen; D055748:SOXB1 Transcription Factors; C527783:Sox2 protein, mouse; D049452:Green Fluorescent Proteins; D010751:Phosphopyruvate Hydratase; D001973:Bromodeoxyuridine