EGFL7 loss correlates with increased VEGF-D expression, upregulating hippocampal adult neurogenesis and improving spatial learning and memory.
Adult neurogenesis
Hippocampus
Neural stem cell
Subgranular zone
Journal
Cellular and molecular life sciences : CMLS
ISSN: 1420-9071
Titre abrégé: Cell Mol Life Sci
Pays: Switzerland
ID NLM: 9705402
Informations de publication
Date de publication:
30 Jan 2023
30 Jan 2023
Historique:
received:
27
10
2022
accepted:
03
01
2023
revised:
28
12
2022
entrez:
30
1
2023
pubmed:
31
1
2023
medline:
2
2
2023
Statut:
epublish
Résumé
Neural stem cells reside in the subgranular zone, a specialized neurogenic niche of the hippocampus. Throughout adulthood, these cells give rise to neurons in the dentate gyrus, playing an important role in learning and memory. Given that these core cognitive processes are disrupted in numerous disease states, understanding the underlying mechanisms of neural stem cell proliferation in the subgranular zone is of direct practical interest. Here, we report that mature neurons, neural stem cells and neural precursor cells each secrete the neurovascular protein epidermal growth factor-like protein 7 (EGFL7) to shape this hippocampal niche. We further demonstrate that EGFL7 knock-out in a Nestin-CreERT2-based mouse model produces a pronounced upregulation of neurogenesis within the subgranular zone. RNA sequencing identified that the increased expression of the cytokine VEGF-D correlates significantly with the ablation of EGFL7. We substantiate this finding with intraventricular infusion of VEGF-D upregulating neurogenesis in vivo and further show that VEGF-D knock-out produces a downregulation of neurogenesis. Finally, behavioral studies in EGFL7 knock-out mice demonstrate greater maintenance of spatial memory and improved memory consolidation in the hippocampus by modulation of pattern separation. Taken together, our findings demonstrate that both EGFL7 and VEGF-D affect neurogenesis in the adult hippocampus, with the ablation of EGFL7 upregulating neurogenesis, increasing spatial learning and memory, and correlating with increased VEGF-D expression.
Identifiants
pubmed: 36715759
doi: 10.1007/s00018-023-04685-z
pii: 10.1007/s00018-023-04685-z
pmc: PMC9886625
doi:
Substances chimiques
Vascular Endothelial Growth Factor D
0
Intercellular Signaling Peptides and Proteins
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
54Subventions
Organisme : Deutsche Forschungsgemeinschaft
ID : SCHM 2159/4-1
Commentaires et corrections
Type : ErratumIn
Informations de copyright
© 2023. The Author(s).
Références
Seki T, Arai Y (1999) Temporal and spacial relationships between PSA-NCAM-expressing, newly generated granule cells, and radial glia-like cells in the adult dentate gyrus. J Comp Neurol 410(3):503–513
pubmed: 10404415
doi: 10.1002/(SICI)1096-9861(19990802)410:3<503::AID-CNE11>3.0.CO;2-H
Barnea A, Nottebohm F (1994) Seasonal recruitment of hippocampal neurons in adult free-ranging black-capped chickadees. Proc Natl Acad Sci U S A 91(23):11217–11221
pubmed: 7972037
pmcid: 45198
doi: 10.1073/pnas.91.23.11217
Kuhn HG, Dickinson-Anson H, Gage FH (1996) Neurogenesis in the dentate gyrus of the adult rat: age-related decrease of neuronal progenitor proliferation. J Neurosci 16(6):2027–2033
pubmed: 8604047
pmcid: 6578509
doi: 10.1523/JNEUROSCI.16-06-02027.1996
Kempermann G, Kuhn HG, Gage FH (1997) More hippocampal neurons in adult mice living in an enriched environment. Nature 386(6624):493–495
pubmed: 9087407
doi: 10.1038/386493a0
Eriksson PS et al (1998) Neurogenesis in the adult human hippocampus. Nat Med 4(11):1313–1317
pubmed: 9809557
doi: 10.1038/3305
Roy NS et al (2000) In vitro neurogenesis by progenitor cells isolated from the adult human hippocampus. Nat Med 6(3):271–277
pubmed: 10700228
doi: 10.1038/73119
Knoth R et al (2010) Murine features of neurogenesis in the human hippocampus across the lifespan from 0 to 100 years. PLoS One 5(1):e8809
pubmed: 20126454
pmcid: 2813284
doi: 10.1371/journal.pone.0008809
Spalding KL et al (2013) Dynamics of hippocampal neurogenesis in adult humans. Cell 153(6):1219–1227
pubmed: 23746839
pmcid: 4394608
doi: 10.1016/j.cell.2013.05.002
Boldrini M et al (2018) Human hippocampal neurogenesis persists throughout aging. Cell Stem Cell 22(4):589–599585
pubmed: 29625071
pmcid: 5957089
doi: 10.1016/j.stem.2018.03.015
Ming GL, Song H (2011) Adult neurogenesis in the mammalian brain: significant answers and significant questions. Neuron 70(4):687–702
pubmed: 21609825
pmcid: 3106107
doi: 10.1016/j.neuron.2011.05.001
Kang E, Wen Z, Song H, Christian KM, Ming GL (2016) Adult neurogenesis and psychiatric disorders. Cold Spring Harb Perspect Biol. https://doi.org/10.1101/cshperspect.a019026
doi: 10.1101/cshperspect.a019026
pubmed: 26801682
pmcid: 5008067
Anacker C, Hen R (2017) Adult hippocampal neurogenesis and cognitive flexibility - linking memory and mood. Nat Rev Neurosci 18(6):335–346
pubmed: 28469276
pmcid: 6261347
doi: 10.1038/nrn.2017.45
Kempermann G et al (2018) Human adult neurogenesis: evidence and remaining questions. Cell Stem Cell 23(1):25–30
pubmed: 29681514
pmcid: 6035081
doi: 10.1016/j.stem.2018.04.004
Berdugo-Vega G et al (2020) Increasing neurogenesis refines hippocampal activity rejuvenating navigational learning strategies and contextual memory throughout life. Nat Commun 11(1):135
pubmed: 31919362
pmcid: 6952376
doi: 10.1038/s41467-019-14026-z
Kempermann G, Jessberger S, Steiner B, Kronenberg G (2004) Milestones of neuronal development in the adult hippocampus. Trends Neurosci 27(8):447–452
pubmed: 15271491
doi: 10.1016/j.tins.2004.05.013
Lima SMA, Gomes-Leal W (2019) Neurogenesis in the hippocampus of adult humans: controversy “fixed” at last. Neural Regen Res 14(11):1917–1918
pubmed: 31290449
pmcid: 6676862
doi: 10.4103/1673-5374.259616
Yoon K, Gaiano N (2005) Notch signaling in the mammalian central nervous system: insights from mouse mutants. Nat Neurosci 8(6):709–715
pubmed: 15917835
doi: 10.1038/nn1475
Zhang R, Engler A, Taylor V (2018) Notch: an interactive player in neurogenesis and disease. Cell Tissue Res 371(1):73–89
pubmed: 28620760
doi: 10.1007/s00441-017-2641-9
Stump G et al (2002) Notch1 and its ligands Delta-like and Jagged are expressed and active in distinct cell populations in the postnatal mouse brain. Mech Dev 114(1–2):153–159
pubmed: 12175503
doi: 10.1016/S0925-4773(02)00043-6
Ables JL, Breunig JJ, Eisch AJ, Rakic P (2011) Not(ch) just development: Notch signalling in the adult brain. Nat Rev Neurosci 12(5):269–283
pubmed: 21505516
pmcid: 3159580
doi: 10.1038/nrn3024
Ehm O et al (2010) RBPJkappa-dependent signaling is essential for long-term maintenance of neural stem cells in the adult hippocampus. J Neurosci 30(41):13794–13807
pubmed: 20943920
pmcid: 6633732
doi: 10.1523/JNEUROSCI.1567-10.2010
Kopan R, Ilagan MX (2009) The canonical Notch signaling pathway: unfolding the activation mechanism. Cell 137(2):216–233
pubmed: 19379690
pmcid: 2827930
doi: 10.1016/j.cell.2009.03.045
Bicker F, Schmidt MHH (2010) EGFL7: a new player in homeostasis of the nervous system. Cell Cycle 9(7):1263–1269
pubmed: 20372059
doi: 10.4161/cc.9.7.11091
Larochelle C et al (2018) EGFL7 reduces CNS inflammation in mouse. Nat Commun 9(1):819
pubmed: 29483510
pmcid: 5827652
doi: 10.1038/s41467-018-03186-z
Nikolic I et al (2013) EGFL7 ligates alphavbeta3 integrin to enhance vessel formation. Blood 121(15):3041–3050
pubmed: 23386126
doi: 10.1182/blood-2011-11-394882
Jolivel V et al (2015) Perivascular microglia promote blood vessel disintegration in the ischemic penumbra. Acta Neuropathol 129(2):279–295
pubmed: 25500713
doi: 10.1007/s00401-014-1372-1
Schmidt MHH et al (2009) Epidermal growth factor-like domain 7 (EGFL7) modulates Notch signalling and affects neural stem cell renewal. Nat Cell Biol 11(7):873–880
pubmed: 19503073
doi: 10.1038/ncb1896
Bicker F et al (2017) Neurovascular EGFL7 regulates adult neurogenesis in the subventricular zone and thereby affects olfactory perception. Nat Commun 8:15922
pubmed: 28656980
pmcid: 5493759
doi: 10.1038/ncomms15922
Artegiani B et al (2017) A single-cell RNA sequencing study reveals cellular and molecular dynamics of the hippocampal neurogenic niche. Cell Rep 21(11):3271–3284
pubmed: 29241552
doi: 10.1016/j.celrep.2017.11.050
Shin J et al (2015) Single-cell RNA-Seq with waterfall reveals molecular cascades underlying adult neurogenesis. Cell Stem Cell 17(3):360–372
pubmed: 26299571
pmcid: 8638014
doi: 10.1016/j.stem.2015.07.013
Brandt MD, Hubner M, Storch A (2012) Brief report: adult hippocampal precursor cells shorten S-phase and total cell cycle length during neuronal differentiation. Stem Cells 30(12):2843–2847
pubmed: 22987479
doi: 10.1002/stem.1244
Vicidomini C, Guo N, Sahay A (2020) Communication, cross talk, and signal integration in the adult hippocampal neurogenic niche. Neuron 105(2):220–235
pubmed: 31972145
pmcid: 7184932
doi: 10.1016/j.neuron.2019.11.029
Li Y, Guo W (2021) Neural stem cell niche and adult neurogenesis. Neuroscientist 27(3):235–245
pubmed: 32729779
doi: 10.1177/1073858420939034
Lois C, Garcia-Verdugo JM, Alvarez-Buylla A (1996) Chain migration of neuronal precursors. Science 271(5251):978–981
pubmed: 8584933
doi: 10.1126/science.271.5251.978
Peretto P, Merighi A, Fasolo A, Bonfanti L (1997) Glial tubes in the rostral migratory stream of the adult rat. Brain Res Bull 42(1):9–21
pubmed: 8978930
doi: 10.1016/S0361-9230(96)00116-5
Lledo PM, Merkle FT, Alvarez-Buylla A (2008) Origin and function of olfactory bulb interneuron diversity. Trends Neurosci 31(8):392–400
pubmed: 18603310
pmcid: 4059175
doi: 10.1016/j.tins.2008.05.006
Toda T, Parylak SL, Linker SB, Gage FH (2019) The role of adult hippocampal neurogenesis in brain health and disease. Mol Psychiatry 24(1):67–87
pubmed: 29679070
doi: 10.1038/s41380-018-0036-2
Mauceri D et al (2020) Nasally delivered VEGFD mimetics mitigate stroke-induced dendrite loss and brain damage. Proc Natl Acad Sci U S A 117(15):8616–8623
pubmed: 32229571
pmcid: 7165430
doi: 10.1073/pnas.2001563117
Han J et al (2015) Vascular endothelial growth factor receptor 3 controls neural stem cell activation in mice and humans. Cell Rep 10(7):1158–1172
pubmed: 25704818
pmcid: 4685253
doi: 10.1016/j.celrep.2015.01.049
Xie Q et al (2019) Treadmill exercise ameliorates focal cerebral ischemia/reperfusion-induced neurological deficit by promoting dendritic modification and synaptic plasticity via upregulating caveolin-1/VEGF signaling pathways. Exp Neurol 313:60–78
pubmed: 30552877
doi: 10.1016/j.expneurol.2018.12.005
Han W et al (2017) VEGF regulates hippocampal neurogenesis and reverses cognitive deficits in immature rats after status epilepticus through the VEGF R2 signaling pathway. Epilepsy Behav 68:159–167
pubmed: 28193596
doi: 10.1016/j.yebeh.2016.12.007
Pombero A, Garcia-Lopez R, Estirado A, Martinez S (2018) Vascular pattern of the dentate gyrus is regulated by neural progenitors. Brain Struct Funct 223(4):1971–1987
pubmed: 29306978
Lin R et al (2019) Systemic factors trigger vasculature cells to drive notch signaling and neurogenesis in neural stem cells in the adult brain. Stem Cells 37(3):395–406
pubmed: 30431198
doi: 10.1002/stem.2947
Jessberger S et al (2009) Dentate gyrus-specific knockdown of adult neurogenesis impairs spatial and object recognition memory in adult rats. Learn Mem 16(2):147–154
pubmed: 19181621
pmcid: 2661246
doi: 10.1101/lm.1172609
Kalm M, Karlsson N, Nilsson MK, Blomgren K (2013) Loss of hippocampal neurogenesis, increased novelty-induced activity, decreased home cage activity, and impaired reversal learning one year after irradiation of the young mouse brain. Exp Neurol 247:402–409
pubmed: 23333566
doi: 10.1016/j.expneurol.2013.01.006
Garthe A, Roeder I, Kempermann G (2016) Mice in an enriched environment learn more flexibly because of adult hippocampal neurogenesis. Hippocampus 26(2):261–271
pubmed: 26311488
doi: 10.1002/hipo.22520
Kempermann G (2019) Environmental enrichment, new neurons and the neurobiology of individuality. Nat Rev Neurosci 20(4):235–245
pubmed: 30723309
doi: 10.1038/s41583-019-0120-x
Lepousez G, Nissant A, Lledo PM (2015) Adult neurogenesis and the future of the rejuvenating brain circuits. Neuron 86(2):387–401
pubmed: 25905812
doi: 10.1016/j.neuron.2015.01.002
Mirochnic S, Wolf S, Staufenbiel M, Kempermann G (2009) Age effects on the regulation of adult hippocampal neurogenesis by physical activity and environmental enrichment in the APP23 mouse model of Alzheimer disease. Hippocampus 19(10):1008–1018
pubmed: 19219917
doi: 10.1002/hipo.20560
Jain S et al (2012) Arf4 determines dentate gyrus-mediated pattern separation by regulating dendritic spine development. PLoS One 7(9):e46340
pubmed: 23050017
pmcid: 3457985
doi: 10.1371/journal.pone.0046340
Akers KG et al (2014) Hippocampal neurogenesis regulates forgetting during adulthood and infancy. Science 344(6184):598–602
pubmed: 24812394
doi: 10.1126/science.1248903
Franjic D et al (2022) Transcriptomic taxonomy and neurogenic trajectories of adult human, macaque, and pig hippocampal and entorhinal cells. Neuron 110(3):452-469e414
pubmed: 34798047
doi: 10.1016/j.neuron.2021.10.036
Schmidt M et al (2007) EGFL7 regulates the collective migration of endothelial cells by restricting their spatial distribution. Development 134(16):2913–2923
pubmed: 17626061
doi: 10.1242/dev.002576
Lakso M et al (1996) Efficient in vivo manipulation of mouse genomic sequences at the zygote stage. Proc Natl Acad Sci U S A 93(12):5860–5865
pubmed: 8650183
pmcid: 39152
doi: 10.1073/pnas.93.12.5860
Corsini NS et al (2009) The death receptor CD95 activates adult neural stem cells for working memory formation and brain repair. Cell Stem Cell 5(2):178–190
pubmed: 19664992
doi: 10.1016/j.stem.2009.05.004
Baldwin ME et al (2005) Vascular endothelial growth factor D is dispensable for development of the lymphatic system. Mol Cell Biol 25(6):2441–2449
pubmed: 15743836
pmcid: 1061605
doi: 10.1128/MCB.25.6.2441-2449.2005
Codega P et al (2014) Prospective identification and purification of quiescent adult neural stem cells from their in vivo niche. Neuron 82(3):545–559
pubmed: 24811379
pmcid: 4360885
doi: 10.1016/j.neuron.2014.02.039
Feng G et al (2000) Imaging neuronal subsets in transgenic mice expressing multiple spectral variants of GFP. Neuron 28(1):41–51
pubmed: 11086982
doi: 10.1016/S0896-6273(00)00084-2
Jaeger BN et al (2020) Miniaturization of smart-seq2 for single-cell and single-nucleus RNA sequencing. STAR Protoc 1(2):100081
pubmed: 33000004
pmcid: 7501729
doi: 10.1016/j.xpro.2020.100081
Leinonen R, Sugawara H, Shumway M, International Nucleotide Sequence Database C (2011) The sequence read archive. Nucleic Acids Res 39:D19–D21
pubmed: 21062823
doi: 10.1093/nar/gkq1019