Skip to main content
SpringerLink
Log in

Vascular pattern of the dentate gyrus is regulated by neural progenitors

Brain Structure and Function Aims and scope Submit manuscript

Cite this article

Abstract

Neurogenesis is a vital process that begins during early embryonic development and continues until adulthood, though in the latter case, it is restricted to the subventricular zone and the subgranular zone of the dentate gyrus (DG). In particular, the DG’s neurogenic properties are structurally and functionally unique, which may be related to its singular vascular pattern. Neurogenesis and angiogenesis share molecular signals and act synergistically, supporting the concept of a neurogenic niche as a functional unit between neural precursors cells and their environment, in which the blood vessels play an important role. Whereas it is well known that vascular development controls neural proliferation in the embryonary and in the adult brain, by releasing neurotrophic factors; the potential influence of neural cells on vascular components during angiogenesis is largely unknown. We have demonstrated that the reduction of neural progenitors leads to a significant impairment of vascular development. Since VEGF is a potential regulator in the neurogenesis–angiogenesis crosstalk, we were interested in assessing the possible role of this molecule in the hippocampal neurovascular development. Our results showed that VEGF is the molecule involved in the regulation of vascular development by neural progenitor cells in the DG.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7

References

  • Alon T, Hemo I, Itin A et al (1995) Vascular endothelial growth factor acts as a survival factor for newly formed retinal vessels and has implications for retinopathy of prematurity. Nat Med 1:1024–1028

    Article  CAS  PubMed  Google Scholar 

  • Asai T, Wanaka A, Kato H et al (1993) Differential expression of two members of FGF receptor gene family, FGFR-1 and FGFR-2 mRNA, in the adult rat central nervous system. Brain Res Mol Brain Res 17:174–178

    Article  CAS  PubMed  Google Scholar 

  • Baffert F, Le T, Sennino B et al (2006) Cellular changes in normal blood capillaries undergoing regression after inhibition of VEGF signaling. Am J Physiol Heart Circ Physiol 290:H547–H559

    Article  CAS  PubMed  Google Scholar 

  • Benjamin LE, Golijanin D, Itin A et al (1999) Selective ablation of immature blood vessels in established human tumors follows vascular endothelial growth factor withdrawal. J Clin Invest 103:159–165

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Boström M, Hellström Erkenstam N, Kaluza D et al (2014) The hippocampal neurovascular niche during normal development and after irradiation to the juvenile mouse brain. Int J Radiat Biol 90:778–789

    Article  PubMed  Google Scholar 

  • Breier G, Albrecht U, Sterrer S, Risau W (1992) Expression of vascular endothelial growth factor during embryonic angiogenesis and endothelial cell differentiation. Development 114:521–532

    CAS  PubMed  Google Scholar 

  • Brown WR (2010) A review of string vessels or collapsed, empty basement membrane tubes. J Alzheimers Dis 21:725–739

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Capela A, Temple S (2002) LeX/ssea-1 is expressed by adult mouse CNS stem cells, identifying them as nonependymal. Neuron 35:865–875

    Article  PubMed  Google Scholar 

  • Chen Q, Jiang L, Li C et al (2012) Haemodynamics-driven developmental pruning of brain vasculature in zebrafish. PLoS Biol 10:e1001374

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Corada M, Nyqvist D, Orsenigo F et al (2010) The Wnt/beta-catenin pathway modulates vascular remodeling and specification by upregulating Dll4/Notch signaling. Dev Cell 18:938–949

    Article  CAS  PubMed  Google Scholar 

  • Craig CG, D’sa R, Morshead CM et al (1999) Migrational analysis of the constitutively proliferating subependyma population in adult mouse forebrain. Neuroscience 93:1197–1206

    Article  CAS  PubMed  Google Scholar 

  • Daneman R, Agalliu D, Zhou L et al (2009) Wnt/ -catenin signaling is required for CNS, but not non-CNS, angiogenesis. Proc Natl Acad Sci 106:641–646

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Dvorak H (2006) Discovery of vascular permeability factor (VPF). Exp Cell Res 312:522–526

  • Fabel K, Fabel K, Tam B et al (2003) VEGF is necessary for exercise-induced adult hippocampal neurogenesis. Eur J Neurosci 18:2803–2812

    Article  PubMed  Google Scholar 

  • Filippov V, Kronenberg G, Pivneva T et al (2003) Subpopulation of nestin-expressing progenitor cells in the adult murine hippocampus shows electrophysiological and morphological characteristics of astrocytes. Mol Cell Neurosci 23:373–382

    Article  CAS  PubMed  Google Scholar 

  • Flamme I, Breier G, Risau W (1995) Vascular endothelial growth factor (VEGF) and VEGF receptor 2 (flk-1) are expressed during vasculogenesis and vascular differentiation in the quail embryo. Dev Biol 169:699–712

    Article  CAS  PubMed  Google Scholar 

  • Franco CA, Jones ML, Bernabeu MO et al (2015) Correction: dynamic endothelial cell rearrangements drive developmental vessel regression. PLoS Biol 13:e1002163

    Article  PubMed  PubMed Central  Google Scholar 

  • Fuentealba LC, Obernier K, Alvarez-Buylla A (2012) Adult neural stem cells bridge their niche. Cell Stem Cell 10:698–708

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Gerhardt H, Golding M, Fruttiger M et al (2003) VEGF guides angiogenic sprouting utilizing endothelial tip cell filopodia. J Cell Biol 161:1163–1177

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Gerhardt H, Ruhrberg C, Abramsson A et al (2004) Neuropilin-1 is required for endothelial tip cell guidance in the developing central nervous system. Dev Dyn 231:503–509

    Article  CAS  PubMed  Google Scholar 

  • Goldman SA, Chen Z (2011) Perivascular instruction of cell genesis and fate in the adult brain. Nat Neurosci 14:1382–1389

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Gould E (1999) Neurogenesis in the Neocortex of Adult Primates. Science 286:548–552

    Article  CAS  PubMed  Google Scholar 

  • Gould E, Reeves AJ, Fallah M et al (1999) Hippocampal neurogenesis in adult Old World primates. Proc Natl Acad Sci 96:5263–5267

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Graus-Porta D, Blaess S, Senften M et al (2001) Beta1-class integrins regulate the development of laminae and folia in the cerebral and cerebellar cortex. Neuron 31:367–379

    Article  CAS  PubMed  Google Scholar 

  • Groppa E, Brkic S, Bovo E et al (2015) VEGF dose regulates vascular stabilization through Semaphorin3A and the Neuropilin-1 + monocyte/TGF-β1 paracrine axis. EMBO Mol Med 7:1366–1384

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Gu C, Yoshida Y, Livet J et al (2005) Semaphorin 3E and plexin-D1 control vascular pattern independently of neuropilins. Science 307:265–268

    Article  CAS  PubMed  Google Scholar 

  • Heuchan AM, Evans N, Henderson-Smart DJ, Simpson JM (2002) Perinatal risk factors for major intraventricular haemorrhage in the australian and new zealand noenatal network, 1005–97. Arch Dis Child Fetal Neoanatal Ed 86:F86–F90

    Article  CAS  Google Scholar 

  • Hofmann G, Balgooyen L, Mattis J et al (2016) Hilar somatostatin interneuron loss reduces dentate gyrus inhibition in a mouse model of temporal lobe epilepsy. Epilepsia 57:977–983

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Inai T, Mancuso M, Hashizume H et al (2004) Inhibition of vascular endothelial growth factor (VEGF) signaling in cancer causes loss of endothelial fenestrations, regression of tumor vessels, and appearance of basement membrane ghosts. Am J Pathol 165:35–52

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Jakeman LB, Armanini M, Phillips HS, Ferrara N (1993) Developmental expression of binding sites and messenger ribonucleic acid for vascular endothelial growth factor suggests a role for this protein in vasculogenesis and angiogenesis. Endocrinology 133:848–859

    Article  CAS  PubMed  Google Scholar 

  • Jiao Q, Xie W-L, Wang Y-Y et al (2013) Spatial relationship between NSCs/NPCs and microvessels in rat brain along prenatal and postnatal development. Int J Dev Neurosci 31:280–285

    Article  PubMed  Google Scholar 

  • Jin K, Zhu Y, Sun Y et al (2002) Vascular endothelial growth factor (VEGF) stimulates neurogenesis in vitro and in vivo. Proc Natl Acad Sci USA 99:11946–11950

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kang W, Hebert JM (2015) FGF Signaling Is Necessary for Neurogenesis in Young Mice and Sufficient to Reverse Its Decline in Old Mice. J Neurosci 35:10217–10223

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Koch S, Claesson-Welsh L (2012) Signal transduction by vascular endothelial growth factor receptors. Cold Spring Harb Perspect Med 2:a006502

    Article  PubMed  PubMed Central  Google Scholar 

  • Kokovay E, Goderie S, Wang Y et al (2010) Adult SVZ lineage cells home to and leave the vascular niche via differential responses to SDF1/CXCR4 signaling. Cell Stem Cell 7:163–173

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Korn C, Augustin HG (2015) Mechanisms of vessel pruning and regression. Dev Cell 34:5–17

    Article  CAS  PubMed  Google Scholar 

  • Korn C, Scholz B, Hu J et al (2014) Endothelial cell-derived non-canonical Wnt ligands control vascular pruning in angiogenesis. Development 141:1757–1766

    Article  CAS  PubMed  Google Scholar 

  • 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 16:2027–2033

    Article  CAS  PubMed  Google Scholar 

  • Leventhal C, Rafii S, Rafii D et al (1999) Endothelial trophic support of neuronal production and recruitment from the adult mammalian subependyma. Mol Cell Neurosci 13:450–464

    Article  CAS  PubMed  Google Scholar 

  • Liang H, Hippenmeyer S, Ghashghaei HT (2012) A Nestin-cre transgenic mouse is insufficient for recombination in early embryonic neural progenitors. Biol Open 1:1200–1203

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Licht T, Keshet E (2015) The vascular niche in adult neurogenesis. Mech Dev 138 Pt 1:56–62

    Article  Google Scholar 

  • Lobov IB, Rao S, Carroll TJ et al (2005) WNT7b mediates macrophage-induced programmed cell death in patterning of the vasculature. Nature 437:417–421

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Louissaint A Jr, Rao S, Leventhal C, Goldman SA (2002) Coordinated interaction of neurogenesis and angiogenesis in the adult songbird brain. Neuron 34:945–960

    Article  CAS  PubMed  Google Scholar 

  • Lu X, Le Noble F, Yuan L et al (2004) The netrin receptor UNC5B mediates guidance events controlling morphogenesis of the vascular system. Nature 432:179–186

    Article  CAS  PubMed  Google Scholar 

  • Luskin MB, Scott Boone M (1994) Rate and pattern of migration of lineally-related olfactory bulb interneurons generated postnatally in the subventricular zone of the rat. Chem Senses 19:695–714

    Article  CAS  PubMed  Google Scholar 

  • Ma S, Huang Z (2015) Neural regulation of CNS angiogenesis during development. Front Biol 10:61–73

    Article  CAS  Google Scholar 

  • Ma S, Kwon HJ, Johng H et al (2013) Radial glial neural progenitors regulate nascent brain vascular network stabilization via inhibition of Wnt signaling. PLoS Biol 11:e1001469

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Matsuzaki H (2000) VEGF rescues hippocampal neurons from glutamate-induced toxicity through Akt and ERK activation. Neurosci Res 38:S51

    Article  Google Scholar 

  • Matsuzaki H, Tamatani M, Yamaguchi A et al (2001) Vascular endothelial growth factor rescues hippocampal neurons from glutamate-induced toxicity: signal transduction cascades. FASEB J 15:1218–1220

    Article  CAS  PubMed  Google Scholar 

  • Meadows KN, Bryant P, Pumiglia K (2001) Vascular endothelial growth factor induction of the angiogenic phenotype requires Ras activation. J Biol Chem 276:49289–49298

    Article  CAS  PubMed  Google Scholar 

  • Meeson AP, Argilla M, Ko K et al (1999) VEGF deprivation-induced apoptosis is a component of programmed capillary regression. Development 126:1407–1415

    CAS  PubMed  Google Scholar 

  • Monje ML, Mizumatsu S, Fike JR, Palmer TD (2002) Irradiation induces neural precursor-cell dysfunction. Nat Med 8:955–962

    Article  CAS  PubMed  Google Scholar 

  • Ng Y-S, Rohan R, Sunday ME et al (2001) Differential expression of VEGF isoforms in mouse during development and in the adult. Dev Dyn 220:112–121

  • Ohkubo Y, Uchida AO, Shin D et al (2004) Fibroblast growth factor receptor 1 is required for the proliferation of hippocampal progenitor cells and for hippocampal growth in mouse. J Neurosci 24:6057–6069

    Article  CAS  PubMed  Google Scholar 

  • Palmer TD, Willhoite AR, Gage FH (2000) Vascular niche for adult hippocampal neurogenesis. J Comp Neurol 425:479–494

    Article  CAS  PubMed  Google Scholar 

  • Phng L-K, Potente M, Leslie JD et al (2009) Nrarp coordinates endothelial Notch and Wnt signaling to control vessel density in angiogenesis. Dev Cell 16:70–82

    Article  CAS  PubMed  Google Scholar 

  • Plate KH, Breier G, Farrell CL, Risau W (1992) Platelet-derived growth factor receptor-beta is induced during tumor development and upregulated during tumor progression in endothelial cells in human gliomas. Lab Invest 67:529–534

    CAS  PubMed  Google Scholar 

  • Pombero A, Garcia-Lopez R, Martinez S (2016) Brain mesenchymal stem cells: physiology and pathological implications. Dev Growth Differ 58:469–480

    Article  PubMed  Google Scholar 

  • Proctor JM, Zang K, Wang D et al (2005) Vascular development of the brain requires beta8 integrin expression in the neuroepithelium. J Neurosci 25:9940–9948

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Qian X, Shen Q, Goderie SK et al (2000) Timing of CNS Cell Generation. Neuron 28:69–80

    Article  CAS  PubMed  Google Scholar 

  • Raab S, Beck H, Gaumann A et al (2004) Impaired brain angiogenesis and neuronal apoptosis induced by conditional homozygous inactivation of vascular endothelial growth factor. Thromb Haemost 91:595–605

    CAS  PubMed  Google Scholar 

  • Rao S, Lobov IB, Vallance JE et al (2007) Obligatory participation of macrophages in an angiopoietin 2-mediated cell death switch. Development 134:4449–4458

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Reichardt LF (2006) Neurotrophin-regulated signalling pathways. Philos Trans R Soc Lond B Biol Sci 361:1545–1564

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Rickmann M, Amaral DG, Cowan WM (1987) Organization of radial glial cells during the development of the rat dentate gyrus. J Comp Neurol 264:449–479

    Article  CAS  PubMed  Google Scholar 

  • Riquelme PA, Drapeau E, Doetsch F (2008) Brain micro-ecologies: neural stem cell niches in the adult mammalian brain. Philos Trans R Soc Lond B Biol Sci 363:123–137

    Article  PubMed  Google Scholar 

  • Ruhrberg C (2003) Growing and shaping the vascular tree: multiple roles for VEGF. BioEssays 25:1052–1060

    Article  CAS  PubMed  Google Scholar 

  • Ruhrberg C, Gerhardt H, Golding M et al (2002) Spatially restricted patterning cues provided by heparin-binding VEGF-A control blood vessel branching morphogenesis. Genes Dev 16:2684–2698

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Scott A, Powner MB, Gandhi P et al (2010) Astrocyte-derived vascular endothelial growth factor stabilizes vessels in the developing retinal vasculature. PLoS One 5:e11863

    Article  PubMed  PubMed Central  Google Scholar 

  • Shen Q, Goderie SK, Jin L et al (2004) Endothelial cells stimulate self-renewal and expand neurogenesis of neural stem cells. Science 304:1338–1340

    Article  CAS  PubMed  Google Scholar 

  • Siebzehnrubl FA, Blumcke I (2008) Neurogenesis in the human hippocampus and its relevance to temporal lobe epilepsies. Epilepsia 49(Suppl 5):55–65

    Article  PubMed  Google Scholar 

  • Sondell M, Lundborg G, Kanje M (1999) Vascular endothelial growth factor has neurotrophic activity and stimulates axonal outgrowth, enhancing cell survival and Schwann cell proliferation in the peripheral nervous system. J Neurosci 19:5731–5740

    CAS  PubMed  Google Scholar 

  • Stenman JM, Rajagopal J, Carroll TJ et al (2008) Canonical Wnt signaling regulates organ-specific assembly and differentiation of CNS vasculature. Science 322:1247–1250

    Article  CAS  PubMed  Google Scholar 

  • Stolp HB, Molnár Z (2015) Neurogenic niches in the brain: help and hindrance of the barrier systems. Front Neurosci 9:20

    Article  PubMed  PubMed Central  Google Scholar 

  • Stubbs D, DeProto J, Nie K et al (2009) Neurovascular congruence during cerebral cortical development. Cereb Cortex 19:i32–i41

    Article  PubMed  PubMed Central  Google Scholar 

  • Thakker GD, Hajjar DP, Muller WA, Rosengart TK (1999) The role of phosphatidylinositol 3-kinase in vascular endothelial growth factor signaling. J Biol Chem 274:10002–10007

    Article  CAS  PubMed  Google Scholar 

  • Tortora D, Veverino M, Malova M et al (2018) Differences in subependymal vein anatomy may predispose preterm infants to GMH-IVH. Arch Dis Child Fetal Neonatal Ed 103:F59–F65

    Article  PubMed  Google Scholar 

  • Tronche F, Kellendonk C, Kretz O et al (1999) Disruption of the glucocorticoid receptor gene in the nervous system results in reduced anxiety. Nat Genet 23:99–103

    Article  CAS  PubMed  Google Scholar 

  • Udan RS, Vadakkan TJ, Dickinson ME (2013) Dynamic responses of endothelial cells to changes in blood flow during vascular remodeling of the mouse yolk sac. Development 140:4041–4050

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Urbán N, Guillemot F (2014) Neurogenesis in the embryonic and adult brain: same regulators, different roles. Front Cell Neurosci 8:396

    Article  PubMed  PubMed Central  Google Scholar 

  • Wagner JP, Black IB, DiCicco-Bloom E (1999) Stimulation of neonatal and adult brain neurogenesis by subcutaneous injection of basic fibroblast growth factor. J Neurosci 19:6006–6016

    CAS  PubMed  Google Scholar 

  • Weickert CS, Kittell DA, Saunders RC et al (2005) Basic fibroblast growth factor and fibroblast growth factor receptor-1 in the human hippocampal formation. Neuroscience 131:219–233

    Article  CAS  PubMed  Google Scholar 

  • Wu LW, Mayo LD, Dunbar JD et al (2000) VRAP is an adaptor protein that binds KDR, a receptor for vascular endothelial cell growth factor. J Biol Chem 275:6059–6062

    Article  CAS  PubMed  Google Scholar 

  • Xiao Z, Kong Y, Yang S et al (2007) Upregulation of Flk-1 by bFGF via the ERK pathway is essential for VEGF-mediated promotion of neural stem cell proliferation. Cell Res 17:73–79

    Article  CAS  PubMed  Google Scholar 

  • Xu X, Qiao W, Li C, Deng C (2002) Generation of Fgfr1 conditional knockout mice. Genesis 32:85–86

    Article  PubMed  Google Scholar 

  • Yamashima T, Tonchev AB, Vachkov IH et al (2004) Vascular adventitia generates neuronal progenitors in the monkey hippocampus after ischemia. Hippocampus 14:861–875

    Article  PubMed  Google Scholar 

  • Yancopoulos GD, Davis S, Gale NW et al (2000) Vascular-specific growth factors and blood vessel formation. Nature 407:242–248

    Article  CAS  PubMed  Google Scholar 

  • Zachary I (2001) Signaling mechanisms mediating vascular protective actions of vascular endothelial growth factor. Am J Physiol Cell Physiol 280:C1375–C1386

    Article  CAS  PubMed  Google Scholar 

  • Zhao C, Deng W, Gage FH (2008) Mechanisms and functional implications of adult neurogenesis. Cell 132:645–660

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

We thank Dr. A. Barco for providing us Nes-Cre mouse strain. This work was supported by Spanish State Research Agency, through the “Severo Ochoa” Program for Centers of Excellence in R&D (ref. SEV- 2013-0317), by Economy and Competitivity Ministry through Fondos FEDER (SAF2014-59347-C2-1-R), by Generalitat Valenciana Prometeo II Grant (2014/014), by Instituto de Salud Carlos III (RD16/001/0010) (Co-funded by European Regional Development Fund/European Social Fund) and Todos con Natalia Niemann Pick C Association (2016/00084/001).

Author information

Author notes

  1. Ana Pombero and Raquel Garcia-Lopez have contributed equally to this work and are listed alphabetically.

Authors and Affiliations

  1. Instituto de Neurociencias, UMH-CSIC, Campus de San Juan, 03550, Alicante, Spain

    Salvador Martinez

  2. IMIB-Arrixaca, University of Murcia, Av. Teniente Flomesta, 5, 30003, Murcia, Spain

    Ana Pombero, Raquel Garcia-Lopez & Alicia Estirado

  3. Centro de Investigación Biomédica En Red en Salud Mental (CIBERSAM), Madrid, Spain

    Salvador Martinez

Authors
  1. Ana Pombero
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Raquel Garcia-Lopez
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Alicia Estirado
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Salvador Martinez
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Salvador Martinez.

Ethics declarations

Funding

This work was supported by Spanish State Research Agency, through the “Severo Ochoa” Program for Centers of Excellence in R&D (ref. SEV- 2013 − 0317), by Economy and Competitivity Ministry through Fondos FEDER (SAF2014-59347-C2-1-R), by Generalitat Valenciana Prometeo II Grant (2014/014), by Instituto de Salud Carlos III (RD16/001/0010) (Co-funded by European Regional Development Fund/European Social Fund), and Todos con Natalia Niemann Pick C Association (2016/00084/001)

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical approval

All animal experimental assays were performed in compliance with the Spanish and European Union laws on animal care in experimentation (Council Directive 86/609/EEC) and approved by the Animal Experimentation Ethics Committee of our University. This article does not contain any studies with human participants performed by any of the authors.

Electronic supplementary material

Below is the link to the electronic supplementary material.

Supplementary Figure 1

. Analysis of cre activity in the cortex and the hippocampus. CD13 (green color) was used as a pericyte marker together with RFP (red color) used as a reporter of cre activity. No double labeling was detected in double immunohistochemistry for CD13/RFP in Cx (A-C), DMS (D-F), CA (G-I), and DG (J-L). Scale bar is 25 µm (TIF 44947 KB)

Rights and permissions

Reprints and Permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Pombero, A., Garcia-Lopez, R., Estirado, A. et al. Vascular pattern of the dentate gyrus is regulated by neural progenitors. Brain Struct Funct 223, 1971–1987 (2018). https://doi.org/10.1007/s00429-017-1603-z

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00429-017-1603-z

Keywords

search

Navigation