Abstract
Neurogenesis occurs during the embryonic period and ceases soon after birth in the neocortex, but continues to occur in the hippocampus even in the adult. The embryonic neocortex has radial glia or progenitor cells expressing brain lipid-binding protein (BLBP), whereas the adult hippocampus has radial granule progenitor cells expressing BLBP and glial fibrillary acidic protein (GFAP) in the subgranular zone. We previously found that embryonic hippocampal granule progenitor cells express GFAP, but not BLBP, indicating that these cells are different from both embryonic neocortical and adult granule progenitor cells. In the present study, as the first step towards understanding the mechanism of persistent hippocampal neurogenesis, we aimed to determine the stage at which embryonic-type granule progenitors become adult-type progenitors using mouse Gfap-GFP transgenic mice. During the embryonic stages, Gfap-GFP-positive (Gfap-GFP+) cells were distributed in the entire developing dentate gyrus (DG), whereas BLBP-positive (BLBP+) cells were mainly present in the fimbria and subpial region, and to some extent in the DG. Up to postnatal day 0 (P0), double-positive cells were scarcely detected. However, at P1, one-third of the Gfap-GFP+ cells in the DG suddenly began to weakly express BLBP. Thereafter, Gfap-GFP+/BLBP+ cells rapidly increased in number, and extended their radial processes in the inner granular cell layer. At P14 and in the adult, two-thirds of the Gfap-GFP+ cells in the subgranular zone showed BLBP immunoreactivity. These results suggest that the properties of hippocampal granule progenitor cells are rapidly altered from an embryonic to adult type soon after birth.
Similar content being viewed by others
Change history
25 January 2018
In the original publication figure parts 8c, 8f, and 8i were mixed up and thus incorrectly labeled. Here is a corrected version with the parts properly labeled
References
Abrous DN, Wojtowicz JM (2015) Interaction between neurogenesis and hippocampal memory system: new vistas. Cold Spring Harb Perspect Biol 7:1–24. doi:10.1101/cshperspect.a018952
Altman J, Bayer SA (1990a) Migration and distribution of two populations of hippocampal granule cell precursors during the perinatal and postnatal periods. J Comp Neurol 301:365–381. doi:10.1002/cne.903010304
Altman J, Bayer SA (1990b) Mosaic organization of the hippocampal neuroepithelium and the multiple germinal sources of dentate granule cells. J Comp Neurol 301:325–342. doi:10.1002/cne.903010302
Altman J, Bayer SA (1990c) Prolonged sojourn of developing pyramidal cells in the intermediate zone of the hippocampus and their settling in the stratum pyramidale. J Comp Neurol 301:343–364. doi:10.1002/cne.903010303
Altman J, Das GD (1965) Autoradiographic and histological evidence of postnatal hippocampal neurogenesis in rats. J Comp Neurol 124:319–335. doi:10.1002/cne.901240303
Anthony TE, Klein C, Fishell G, Heintz N (2004) Radial glia serve as neuronal progenitors in all regions of the central nervous system. Neuron 41:881–890. doi:10.1016/S0896-6273(04)00140-0
Anthony TE, Mason HA, Gridley T, Fishell G, Heintz N (2005) Brain lipid-binding protein is a direct target of Notch signaling in radial glial cells service Brain lipid-binding protein is a direct target of Notch signaling in radial glial cells. Genes Dev 19:1028–1033. doi:10.1101/gad.1302105
Arai Y, Funatsu N, Numayama-Tsuruta K, Nomura T, Nakamura S, Osumi N (2005) Role of Fabp7, a downstream gene of Pax6, in the maintenance of neuroepithelial cells during early embryonic development of the rat cortex. J Neurosci 25:9752–9761. doi:10.1523/JNEUROSCI.2512-05.2005
Barry G, Piper M, Lindwall C, Moldrich R, Mason S, Little E, Sarkar A, Tole S, Gronostajski RM, Richards LJ (2008) Specific glial populations regulate hippocampal morphogenesis. J Neurosci 28:12328–12340. doi:10.1523/JNEUROSCI.4000-08.2008
Belmadani A, Ren D, Bhattacharyya BJ, Rothwangl KB, Hope TJ, Perlman H, Miller RJ (2015) Identification of a sustained neurogenic zone at the dorsal surface of the adult mouse hippocampus and its regulation by the chemokine SDF-1. Hippocampus 25:1224–1241. doi:10.1002/hipo.22428
Bergmann O, Spalding KL, Frisén J (2015) Adult neurogenesis in humans. Cold Spring Harb Perspect Biol 7:a018994. doi:10.1101/cshperspect.a018994
Bowers M, Jessberger S (2016) Linking adult hippocampal neurogenesis with human physiology and disease. Dev Dyn. doi:10.1002/dvdy.24396
Brezun JM, Daszuta A (1999) Depletion in serotonin decreases neurogenesis in the dentate gyrus and the subventricular zone of adult rats. Neuroscience 89:999–1002. doi:10.1016/S0306-4522(98)00693-9
Brunne B, Zhao S, Derouiche A, Herz J, May P, Frotscher M, Bock HH (2010) Origin, maturation, and astroglial transformation of secondary radial glial cells in the developing dentate gyrus. Gila 58:1553–1569. doi:10.1002/glia.21029
Chmurzyñska A (2006) The multigene family of fatty acid-binding proteins (FABPs): function, structure and polymorphism. J Appl Genet 47:39–48. doi:10.1007/BF03194597
Christie KJ, Turnley AM (2013) Regulation of endogenous neural stem/progenitor cells for neural repair-factors that promote neurogenesis and gliogenesis in the normal and damaged brain. Front Cell Neurosci 6:70. doi:10.3389/fncel.2012.00070
Cooper-Kuhn CM, Winkler J, Kuhn HG (2004) Decreased neurogenesis after cholinergic forebrain lesion in the adult rat. J Neurosci Res 77:155–165. doi:10.1002/jnr.20116
Danzer SC (2012) Depression, stress, epilepsy and adult neurogenesis. Exp Neurol 233:22–32. doi:10.1016/j.expneurol.2011.05.023
Drew LJ, Fusi S, Hen R (2013) Adult neurogenesis in the mammalian hippocampus: why the dentate gyrus? Learn Mem 20:710–729. doi:10.1101/lm.026542.112
Eisch AJ, Petrik D (2012) Depression and hippocampal neurogenesis: a road to remission? Science 338:72–75. doi:10.1126/science.1222941
Encinas JM, Vaahtokari A, Enikolopov G (2006) Fluoxetine targets early progenitor cells in the adult brain. Proc Natl Acad Sci USA 103:8233–8238. doi:10.1073/pnas.0601992103
Eriksson PS, Perfilieva E, Bjork-Eriksson T, Alborn AM, Nordborg C, Peterson DA, Gage FH (1998) Neurogenesis in the adult human hippocampus. Nat Med 4:1313–1317. doi:10.1038/3305
Fukuda S, Kato F, Tozuka Y, Yamaguchi M, Miyamoto Y, Hisatsune T (2003) Two distinct subpopulations of nestin-positive cells in adult mouse dentate gyrus. J Neurosci 23:9357–9366
Garcia ADR, Doan NB, Imura T, Bush TG, Sofroniew MV (2004) GFAP-expressing progenitors are the principal source of constitutive neurogenesis in adult mouse forebrain. Nat Neurosci 7:1233–1241. doi:10.1038/nn1340
Georg Kuhn H, Blomgren K (2011) Developmental dysregulation of adult neurogenesis. Eur J Neurosci 33:1115–1122. doi:10.1111/j.1460-9568.2011.07610.x
Gilley JA, Yang CP, Kernie SG (2011) Developmental profiling of postnatal dentate gyrus progenitors provides evidence for dynamic cell-autonomous regulation. Hippocampus 21:33–47. doi:10.1002/hipo.20719
Hartfuss E, Förster E, Bock HH, Hack MA, Leprince P, Luque JM, Herz J, Frotscher M, Götz M (2003) Reelin signaling directly affects radial glia morphology and biochemical maturation. Development 130:4597–4609. doi:10.1242/dev.00654
Hodge RD, Hevner RF (2011) Expression and actions of transcription factors in adult hippocampal neurogenesis. Dev Neurobiol 71:680–689. doi:10.1002/dneu.20882
Hsieh J (2012) Orchestrating transcriptional control of adult neurogenesis. Genes Dev 26:1010–1021. doi:10.1101/gad.187336.112
Ito H, Morishita R, Iwamoto I, Nagata KI (2014) Establishment of an in vivo electroporation method into postnatal newborn neurons in the dentate gyrus. Hippocampus 24:1449–1457. doi:10.1002/hipo.22325
Jessberger S (2016) Neural repair in the adult brain. F1000Research 5:1–8. doi:10.12688/f1000research.7459.1
Kaneko N, Okano H, Sawamoto K (2006) Role of the cholinergic system in regulating survival of newborn neurons in the adult mouse dentate gyrus and olfactory bulb. Genes Cells 11:1145–1159. doi:10.1111/j.1365-2443.2006.01010.x
Keilani S, Sugaya K (2008) Reelin induces a radial glial phenotype in human neural progenitor cells by activation of Notch-I. BMC Dev Biol 8:1–9. doi:10.1186/1471-213X-8-69
Kempermann G (2011) Adult neurogenesis 2. Oxford University Press, Oxford
Kriegstein A, Alvarez-buylla A (2009) The glial nature of embryonic and adult neural stem cells. Annu Rev Neurosci. doi:10.1146/annurev.neuro.051508.135600.The
Lepousez G, Nissant A, Lledo PM (2015) Adult neurogenesis and the future of the rejuvenating brain circuits. Neuron 86:387–401. doi:10.1016/j.neuron.2015.01.002
Li G, Pleasure SJ (2005) Morphogenesis of the dentate gyrus: what we are learning from mouse mutants. Dev Neurosci 27:93–99
Li G, Pleasure SJ (2014) The development of hippocampal cellular assemblies. Wiley Interdiscip Rev Dev Biol 3:165–177
Li G, Kataoka H, Coughlin SR, Pleasure SJ (2009) Identification of a transient subpial neurogenic zone in the developing dentate gyrus and its regulation by Cxcl12 and reelin signaling. Development 136:327–335. doi:10.1242/dev.025742
Li G, Fang L, Fernández G, Pleasure SJ (2013) The ventral hippocampus is the embryonic origin for adult neural stem cells in the dentate gyrus. Neuron 78:658–672. doi:10.1016/j.neuron.2013.03.019
Liu Y, Namba T, Liu J, Suzuki R, Shioda S, Seki T (2010) Glial fibrillary acidic protein-expressing neural progenitors give rise to immature neurons via early intermediate progenitors expressing both glial fibrillary acidic protein and neuronal markers in the adult hippocampus. Neuroscience 166:241–251. doi:10.1016/j.neuroscience.2009.12.026
Malberg JE, Eisch AJ, Nestler EJ, Duman RS (2000) Chronic antidepressant treatment increases neurogenesis in adult rat hippocampus. J Neurosci 20:9104–9110
Matsumata M, Sakayori N, Maekawa M, Owada Y, Yoshikawa T, Osumi N (2012) The effects of Fabp7 and Fabp5 on postnatal hippocampal neurogenesis in the mouse. Stem Cells 30:1532–1543. doi:10.1002/stem.1124
Morrens J, van den Broeck W, Kempermann G (2012) Glial cells in adult neurogenesis. Glia 60:159–174. doi:10.1002/glia.21247
Nakahira E, Yuasa S (2005) Neuronal generation, migration, and differentiation in the mouse hippocampal primoridium as revealed by enhanced green fluorescent protein gene transfer by means of in utero electroporation. J Comp Neurol 483:329–340. doi:10.1002/cne.20441
Namba T, Mochizuki H, Onodera M, Mizuno Y, Namiki H, Seki T (2005) The fate of neural progenitor cells expressing astrocytic and radial glial markers in the postnatal rat dentate gyrus. Eur J Neurosci 22:1928–1941. doi:10.1111/j.1460-9568.2005.04396.x
Namba T, Mochizuki H, Suzuki R, Onodera M, Yamaguchi M, Namiki H, Shioda S, Seki T (2011) Time-lapse imaging reveals symmetric neurogenic cell division of GFAP-expressing progenitors for expansion of postnatal dentate granule neurons. PLoS One. doi:10.1371/journal.pone.0025303
Navaero-Quiroga I, Fernandez-Valdes M, Lin SL, Naegele JR (2006) Postnatal cellular contributions of the hippocampus subventricular zone to the dentate gyrus, corpus callosum, fimbria, and cerebral cortex. J Comp Neurol 497:833–845. doi:10.1002/cne.21037
Nicola Z, Fabel K, Kempermann G (2015) Development of the adult neurogenic niche in the hippocampus of mice. Front Neuroanat 9:53. doi:10.3389/fnana.2015.00053
Ostrem B, Di Lullo E, Kriegstein A (2017) oRGs and mitotic somal translocation—a role in development and disease. Curr Opin Neurobiol 42:61–67. doi:10.1016/j.conb.2016.11.007
Overstreet-Wadiche LS, Bensen AL, Westbrook GL (2006) Delayed development of adult-generated granule cells in dentate gyrus. J Neurosci 26:2326–2334. doi:10.1523/JNEUROSCI.4111-05.2006
Owada Y (2008) Fatty acid binding protein: localization and functional significance in the brain. Tohoku J Exp Med 214:213–220. doi:10.1620/tjem.214.213
Raman L, Kong X, Gilley JA, Kernie SG (2011) Chronic hypoxia impairs murine hippocampal development and depletes the postnatal progenitor pool by attenuating mammalian target of rapamycin signaling. Pediatr Res 70:159–165. doi:10.1203/PDR.0b013e31821f6e75
Raponi E, Agenes F, Delphin C, Assard N, Baudier J, Legraverend C, Deloulme JC (2007) S100B expression defines a state in which GFAP-expressing cells lose their neural stem cell potential and acquire a more mature developmental stage. Glia 55:165–177. doi:10.1002/glia.20445
Schmid RS, Yokota Y, Anton ES (2006) Generation and characterization of brain lipid-binding protein promoter-based transgenic mouse models for the study of radial glia. Glia 53:345–351. doi:10.1002/glia.20274
Seki T, Arai Y (1993) Highly polysialylated neural cell adhesion molecule (NCAM-H) is expressed by newly generated granule cells in the dentate gyrus of the adult rat. J Neurosci 13:2351–2358
Seki T, Namba T, Mochizuki H, Onodera M (2007) Clustering, migration, and neurite formation of neural precursor cells in the adult rat hippocampus. J Comp Neurol 502:275–290. doi:10.1002/cne
Seki T, Sato T, Toda K, Osumi N, Imura T, Shioda S (2014) Distinctive population of Gfap-expressing neural progenitors arising around the dentate notch migrate and form the granule cell layer in the developing hippocampus. J Comp Neurol 522:261–283. doi:10.1002/cne.23460
Seri B, Garcia-Verdugo JM, McEwen BS, Alvarez-Buylla A (2001) Astrocytes give rise to new neurons in the adult mammalian hippocampus. J Neurosci 21:7153–7160
Seri B, García-Verdugo JM, Collado-Morente L, McEwen BS, Alvarez-Buylla A (2004) Cell types, lineage, and architecture of the germinal zone in the adult dentate gyrus. J Comp Neurol 478:359–378. doi:10.1002/cne.20288
Shapiro LA, Wang L, Upadhyaya P, Ribak CE (2011) Seizure-induced increased neurogenesis occurs in the dentate gyrus of aged sprague-dawley rats. Aging Dis 2:286–293
Sharifi K, Morihiro Y, Maekawa M, Yasumoto Y, Hoshi H, Adachi Y, Sawada T, Tokuda N, Kondo H, Yoshikawa T, Suzuki M, Owada Y (2011) FABP7 expression in normal and stab-injured brain cortex and its role in astrocyte proliferation. Histochem Cell Biol 136:501–513. doi:10.1007/s00418-011-0865-4
Snyder JS, Cameron HA (2012) Could adult hippocampal neurogenesis be relevant for human behavior? Behav Brain Res 227:384–390. doi:10.1016/j.bbr.2011.06.024
Steiner B, Kronenberg G, Jessberger S, Brandt MD, Reuter K, Kempermann G (2004) Differential regulation of gliogenesis in the context of adult hippocampal neurogenesis in mice. Glia 46:41–52. doi:10.1002/glia.10337
Storch J, McDermott L (2009) Structural and functional analysis of fatty acid-binding proteins. J Lipid Res 50:S126–S131. doi:10.1194/jlr.R800084-JLR200
Suh H, Consiglio A, Ray J, Sawai T, D’Amour KA, Gage FH (2007) In vivo fate analysis reveals the multipotent and self-renewal capacities of Sox2+ neural stem cells in the adult hippocampus. Cell Stem Cell 1:515–528. doi:10.1016/j.stem.2007.09.002
Suzuki R, Watanabe J, Arata S, Funahashi H, Kikuyama S, Shioda S (2003) A transgenic mouse model for the detailed morphological study of astrocytes. Neurosci Res 47:451–454. doi:10.1016/j.neures.2003.08.008
Tabata H, Yoshinaga S, Nakajima K (2012) Cytoarchitecture of mouse and human subventricular zone in developing cerebral neocortex. Exp Brain Res 216:161–168
Taverna E, Götz M, Huttner WB (2014) The cell biology of neurogenesis: toward an understanding of the development and evolution of the neocortex. Annu Rev Cell Dev Biol 30:465–502. doi:10.1146/annurev-cellbio-101011-155801
Toda T, Homma D, Tokuoka H, Hayakawa I, Sugimoto Y, Ichinose H, Kawasaki H (2013) Birth regulates the initiation of sensory map formation through serotonin signaling. Dev Cell 27:32–46. doi:10.1016/j.devcel.2013.09.002
Treves A, Tashiro A, Witter ME, Moser EI (2008) What is the mammalian dentate gyrus good for? Neuroscience 154:1155–1172. doi:10.1016/j.neuroscience.2008.04.073
Vivar C, van Praag H (2013) Functional circuits of new neurons in the dentate gyrus. Front Neural Circuits 7:15. doi:10.3389/fncir.2013.00015
Watanabe A, Toyota T, Owada Y, Hayashi T, Iwayama Y, Matsumata M, Ishitsuka Y, Nakaya A, Maekawa M, Ohnishi T, Arai R, Sakurai K, Yamada K, Kondo H, Hashimoto K et al (2007) Fabp7 maps to a quantitative trait locus for a schizophrenia endophenotype. PLoS Biol 5:2469–2483. doi:10.1371/journal.pbio.0050297
Winner B, Kohl Z, Gage FH (2011) Neurodegenerative disease and adult neurogenesis. Eur J Neurosci 33:1139–1151. doi:10.1111/j.1460-9568.2011.07613.x
Yamaguchi M, Saito H, Suzuki M, Mori K (2000) Visualization of neurogenesis in the central nervous system using nestin promoterGFP transgenic mice. NeuroReport 11:1991–1996
Yamamoto T, Yamamoto A, Watanabe M, Matsuo T, Yamazaki N, Kataoka M, Terada H, Shinohara Y (2009) Classification of FABP isoforms and tissues based on quantitative evaluation of transcript levels of these isoforms in various rat tissues. Biotechnol Lett 31:1695–1701. doi:10.1007/s10529-009-0065-7
Yuasa S (2001) Development of astrocytes in the mouse hippocampus as tracked by tenascin-C gene expression. Arch Histol Cytol 64:149–158
Acknowledgements
We thank Ryusuke Suzuki for the generation of mGfap-GFP mice. We also thank Dr. Helena Popiel of the Department of International Medical Communications of Tokyo Medical University for editorial review of the manuscript. This work was supported by funding from Japan Society for the Promotion of Science (JSPS) KAKENHI (Grant numbers 22500306, 25430041, and 16K07033).
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Conflict of interest
The authors have no conflicts of interest associated with this study.
Additional information
A correction to this article is available online at https://doi.org/10.1007/s00429-018-1613-5.
Electronic supplementary material
Below is the link to the electronic supplementary material.
429_2017_1499_MOESM1_ESM.tif
Supplemental figure Expression of mGfap-GFP and BLPB at P0.Some mGfap-GFP+ cells express BLBP very weakly, although in most sections mGfap-GFP+/BLBP+ cells are not observed (See Fig. 2). Arrows indicate mGfap-GFP+/BLBP+ cells. Scale bars 50 µm (a-c) (TIFF 8987 kb)
Rights and permissions
About this article
Cite this article
Matsue, K., Minakawa, S., Kashiwagi, T. et al. Dentate granule progenitor cell properties are rapidly altered soon after birth. Brain Struct Funct 223, 357–369 (2018). https://doi.org/10.1007/s00429-017-1499-7
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00429-017-1499-7