Home LiteratureArticle Details
PMID: 16319309 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, Non-P.H.S.

Overexpression of the epidermal growth factor receptor confers migratory properties to nonmigratory postnatal neural progenitors.

Aguirre A, Rizvi TA, Ratner N, Gallo V

Abstract

Approaches to successful cell transplantation therapies for the injured brain involve selecting the appropriate neural progenitor type and optimizing the efficiency of the cell engraftment. Here we show that epidermal growth factor receptor (EGFR) expression enhances postnatal neural progenitor migration in vitro and in vivo. Migratory NG2-expressing (NG2+) progenitor cells of the postnatal subventricular zone (SVZ) express higher EGFR levels than nonmigratory, cortical NG2+ cells. The higher endogenous EGFR expression in SVZ NG2+ cells is causally related with their migratory potential in vitro as well as in vivo after cell engraftment. EGFR overexpression in cortical NG2+ cells by transient transfection converted these cells to a migratory phenotype in vitro and in vivo. Finally, cortical NG2+ cells purified from a transgenic mouse in which the EGFR is overexpressed under the CNP promoter exhibited enhanced migratory capability. These findings reveal a new role for EGFR in the postnatal brain and open new avenues to optimize cell engraftment for brain repair.

MeSH Terms
Animals Animals, Newborn/physiology Antigens/genetics,metabolism,physiology Brain/cytology Cell Movement/physiology Cerebral Cortex/cytology Cerebral Ventricles Epidermal Growth Factor/metabolism ErbB Receptors/genetics,physiology Extracellular Matrix Proteins/physiology Humans Mice Mice, Transgenic Natriuretic Peptide, C-Type/metabolism Neurons/metabolism,physiology,transplantation Phenotype Proteoglycans/genetics,metabolism,physiology Stem Cell Transplantation Stem Cells/metabolism,physiology Transfection
Chemicals
Antigens Extracellular Matrix Proteins Proteoglycans chondroitin sulfate proteoglycan 4 Natriuretic Peptide, C-Type Epidermal Growth Factor ErbB Receptors
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Aguirre Adan
Center for Neuroscience Research, Children's Research Institute, Children's National Medical Center, Washington, DC 20010, USA.
Rizvi Tilat A
Ratner Nancy
Gallo Vittorio
References (60)
60 references, click to expand
  1. RGD peptides induce apoptosis by direct caspase-3 activation.
    Nature. 1999 Feb 11;397(6719):534-9 PMID: 10028971
  2. Epidermal and fibroblast growth factors behave as mitogenic regulators for a single multipotent stem cell-like population from the subventricular region of the adult mouse forebrain.
    J Neurosci. 1999 May 1;19(9):3287-97 PMID: 10212288
  3. Subventricular zone astrocytes are neural stem cells in the adult mammalian brain.
    Cell. 1999 Jun 11;97(6):703-16 PMID: 10380923
  4. Patterns and dynamics of SVZ cell migration in the postnatal forebrain: monitoring living progenitors in slice preparations.
    Neuron. 1999 Jul;23(3):461-72 PMID: 10433259
  5. Neurogenesis and neuronal migration in the neonatal rat forebrain anterior subventricular zone do not require GFAP-positive astrocytes.
    Dev Biol. 1999 Dec 15;216(2):622-34 PMID: 10642797
  6. Mechanisms of progenitor maturation are conserved in the striatum and cortex.
    Dev Neurosci. 2000;22(1-2):7-15 PMID: 10657693
  7. Mammalian neural stem cells.
    Science. 2000 Feb 25;287(5457):1433-8 PMID: 10688783
  8. Cell replacement therapies for central nervous system disorders.
    Nat Neurosci. 2000 Jun;3(6):537-44 PMID: 10816308
  9. What role(s) for TGFalpha in the central nervous system?
    Prog Neurobiol. 2000 Dec;62(5):443-73 PMID: 10869779
  10. The chemotactic and mitogenic effects of platelet-derived growth factor-BB on rat aorta smooth muscle cells are inhibited by basic fibroblast growth factor.
    J Cell Sci. 2000 Aug;113 ( Pt 16):2855-63 PMID: 10910770
  11. NG2-expressing cells in the central nervous system: are they oligodendroglial progenitors?
    J Neurosci Res. 2000 Sep 1;61(5):471-9 PMID: 10956416
  12. Disruption of Eph/ephrin signaling affects migration and proliferation in the adult subventricular zone.
    Nat Neurosci. 2000 Nov;3(11):1091-7 PMID: 11036265
  13. The subventricular zone: source of neuronal precursors for brain repair.
    Prog Brain Res. 2000;127:1-11 PMID: 11142024
  14. Untangling the ErbB signalling network.
    Nat Rev Mol Cell Biol. 2001 Feb;2(2):127-37 PMID: 11252954
  15. Inhibitory role of alpha 6 beta 4-associated erbB-2 and phosphoinositide 3-kinase in keratinocyte haptotactic migration dependent on alpha 3 beta 1 integrin.
    J Cell Biol. 2001 Apr 30;153(3):465-78 PMID: 11331299
  16. Age-dependent effects of secreted Semaphorins 3A, 3F, and 3E on developing hippocampal axons: in vitro effects and phenotype of Semaphorin 3A (-/-) mice.
    Mol Cell Neurosci. 2001 Jul;18(1):26-43 PMID: 11461151
  17. PTEN mutation, EGFR amplification, and outcome in patients with anaplastic astrocytoma and glioblastoma multiforme.
    J Natl Cancer Inst. 2001 Aug 15;93(16):1246-56 PMID: 11504770
  18. EGFRs mediate chemotactic migration in the developing telencephalon.
    Development. 2001 Nov;128(21):4203-16 PMID: 11684657
  19. Slit proteins prevent midline crossing and determine the dorsoventral position of major axonal pathways in the mammalian forebrain.
    Neuron. 2002 Jan 17;33(2):233-48 PMID: 11804571
  20. Deleted in colorectal carcinoma and differentially expressed integrins mediate the directional migration of neural precursors in the rostral migratory stream.
    J Neurosci. 2002 May 1;22(9):3568-79 PMID: 11978833
  21. Regeneration of hippocampal pyramidal neurons after ischemic brain injury by recruitment of endogenous neural progenitors.
    Cell. 2002 Aug 23;110(4):429-41 PMID: 12202033
  22. Expression of the green fluorescent protein in the oligodendrocyte lineage: a transgenic mouse for developmental and physiological studies.
    J Neurosci Res. 2002 Nov 15;70(4):529-45 PMID: 12404507
  23. Subpallial dlx2-expressing cells give rise to astrocytes and oligodendrocytes in the cerebral cortex and white matter.
    J Neurosci. 2002 Nov 15;22(22):9821-30 PMID: 12427838
  24. EGF converts transit-amplifying neurogenic precursors in the adult brain into multipotent stem cells.
    Neuron. 2002 Dec 19;36(6):1021-34 PMID: 12495619
  25. Some glial progenitors in the neonatal subventricular zone migrate through the corpus callosum to the contralateral cerebral hemisphere.
    J Comp Neurol. 2003 Apr 14;458(4):381-8 PMID: 12619072
  26. Genetic determinants of malignancy in a mouse model for oligodendroglioma.
    Cancer Res. 2003 Apr 1;63(7):1589-95 PMID: 12670909
  27. Postnatal NG2 proteoglycan-expressing progenitor cells are intrinsically multipotent and generate functional neurons.
    J Cell Biol. 2003 Apr 14;161(1):169-86 PMID: 12682089
  28. Multiple cell populations in the early postnatal subventricular zone take distinct migratory pathways: a dynamic study of glial and neuronal progenitor migration.
    J Neurosci. 2003 May 15;23(10):4240-50 PMID: 12764112
  29. Prenatal development of the rodent rostral migratory stream.
    J Comp Neurol. 2003 Sep 1;463(4):402-18 PMID: 12836176
  30. Glial progenitors of the neonatal subventricular zone differentiate asynchronously, leading to spatial dispersion of glial clones and to the persistence of immature glia in the adult mammalian CNS.
    Dev Biol. 2004 Jun 1;270(1):200-13 PMID: 15136150
  31. NG2-expressing cells in the subventricular zone are type C-like cells and contribute to interneuron generation in the postnatal hippocampus.
    J Cell Biol. 2004 May 24;165(4):575-89 PMID: 15159421
  32. Neuregulin 1-erbB signaling and the molecular/cellular basis of schizophrenia.
    Nat Neurosci. 2004 Jun;7(6):575-80 PMID: 15162166
  33. Stem cell therapy for human neurodegenerative disorders-how to make it work.
    Nat Med. 2004 Jul;10 Suppl:S42-50 PMID: 15272269
  34. NG2-positive cells in the mouse white and grey matter display distinct physiological properties.
    J Physiol. 2004 Nov 15;561(Pt 1):109-22 PMID: 15358811
  35. Short- and long-range attraction of cortical GABAergic interneurons by neuregulin-1.
    Neuron. 2004 Oct 14;44(2):251-61 PMID: 15473965
  36. Receptor tyrosine kinase ErbB4 modulates neuroblast migration and placement in the adult forebrain.
    Nat Neurosci. 2004 Dec;7(12):1319-28 PMID: 15543145
  37. Postnatal neurogenesis and gliogenesis in the olfactory bulb from NG2-expressing progenitors of the subventricular zone.
    J Neurosci. 2004 Nov 17;24(46):10530-41 PMID: 15548668
  38. Structural alterations of the epidermal growth factor receptor gene in human gliomas.
    Proc Natl Acad Sci U S A. 1992 Apr 1;89(7):2965-9 PMID: 1557402
  39. Role for the epidermal growth factor receptor in neurofibromatosis-related peripheral nerve tumorigenesis.
    Cancer Cell. 2005 Jan;7(1):65-75 PMID: 15652750
  40. Developmental profile of ErbB receptors in murine central nervous system: implications for functional interactions.
    J Neurosci Res. 2005 Mar 1;79(5):584-97 PMID: 15682390
  41. New GABAergic interneurons in the adult neocortex and striatum are generated from different precursors.
    J Cell Biol. 2005 Jan 31;168(3):415-27 PMID: 15684031
  42. Asymmetric distribution of EGFR receptor during mitosis generates diverse CNS progenitor cells.
    Neuron. 2005 Mar 24;45(6):873-86 PMID: 15797549
  43. Autocrine regulation of human urothelial cell proliferation and migration during regenerative responses in vitro.
    Exp Cell Res. 2005 May 15;306(1):216-29 PMID: 15878346
  44. Induction of heparin-binding EGF-like growth factor and activation of EGF receptor in imatinib mesylate-treated squamous carcinoma cells.
    J Cell Physiol. 2005 Nov;205(2):218-27 PMID: 15887238
  45. Stem cells and brain cancer.
    Exp Cell Res. 2005 Jun 10;306(2):323-9 PMID: 15925587
  46. Prospective isolation of late development multipotent precursors whose migration is promoted by EGFR.
    Dev Biol. 2005 Aug 1;284(1):112-25 PMID: 15950215
  47. Amplification, enhanced expression and possible rearrangement of EGF receptor gene in primary human brain tumours of glial origin.
    Nature. 1985 Jan 10-18;313(5998):144-7 PMID: 2981413
  48. Embryonic divergence of oligodendrocyte and astrocyte lineages in developing rat cerebrum.
    J Neurosci. 1988 Nov;8(11):3992-4006 PMID: 3054008
  49. Laminin responsiveness is associated with changes in fibroblast morphology, motility, and anchorage-independent growth: cell system for examining the interaction between laminin and EGF signaling pathways.
    J Cell Physiol. 1995 Sep;164(3):593-604 PMID: 7650067
  50. Proliferative zones of postnatal rat brain express epidermal growth factor receptor mRNA.
    Brain Res. 1995 Jan 23;670(1):157-64 PMID: 7719717
  51. A mutant epidermal growth factor receptor common in human glioma confers enhanced tumorigenicity.
    Proc Natl Acad Sci U S A. 1994 Aug 2;91(16):7727-31 PMID: 8052651
  52. In vivo growth factor expansion of endogenous subependymal neural precursor cell populations in the adult mouse brain.
    J Neurosci. 1996 Apr 15;16(8):2649-58 PMID: 8786441
  53. Prenatal ontogeny of the epidermal growth factor receptor and its ligand, transforming growth factor alpha, in the rat brain.
    J Comp Neurol. 1997 Apr 7;380(2):243-61 PMID: 9100135
  54. Epidermal growth factor and fibroblast growth factor-2 have different effects on neural progenitors in the adult rat brain.
    J Neurosci. 1997 Aug 1;17(15):5820-9 PMID: 9221780
  55. Response diversity and the timing of progenitor cell maturation are regulated by developmental changes in EGFR expression in the cortex.
    Neuron. 1997 Aug;19(2):251-67 PMID: 9292717
  56. EGF receptor regulation of cell motility: EGF induces disassembly of focal adhesions independently of the motility-associated PLCgamma signaling pathway.
    J Cell Sci. 1998 Mar;111 ( Pt 5):615-24 PMID: 9454735
  57. Expression of an oncogenic mutant EGF receptor markedly increases the sensitivity of cells to an EGF-receptor-specific antibody-toxin.
    Int J Cancer. 1998 Mar 16;75(6):878-84 PMID: 9506533
  58. Specific, irreversible inactivation of the epidermal growth factor receptor and erbB2, by a new class of tyrosine kinase inhibitor.
    Proc Natl Acad Sci U S A. 1998 Sep 29;95(20):12022-7 PMID: 9751783
  59. Integrins induce activation of EGF receptor: role in MAP kinase induction and adhesion-dependent cell survival.
    EMBO J. 1998 Nov 16;17(22):6622-32 PMID: 9822606
  60. A constitutively active epidermal growth factor receptor cooperates with disruption of G1 cell-cycle arrest pathways to induce glioma-like lesions in mice.
    Genes Dev. 1998 Dec 1;12(23):3675-85 PMID: 9851974
Article Info
Journal
The Journal of neuroscience : the official journal of the Society for Neuroscience
Abbr.
J Neurosci
ISSN
1529-2401
Published
2005-11-30
Pages
11092-106
Language
English
Region
United States
NLM ID
8102140
PMCID
PMC6725641
Subset
IM
Grants
NINDS NIH HHS · R01 NS045702 · United States
NICHD NIH HHS · P30 HD040677 · United States
NINDS NIH HHS · R01NS028840 · United States
NINDS NIH HHS · R01NS045702 · United States
NICHD NIH HHS · P30HD40677 · United States
NINDS NIH HHS · R01 NS028840 · United States
Analysis Services
Analysis Services

Contact

No. 2 Wenbo Road, Zhangqiu District, Jinan, Shandong

Qilu Normal University · Genelibs Bioinformatics Lab

750 Shunhua Rd, Jinan

2F, Bldg F, University Science Park

Tel: 0531-88819269

WeChat Official Account

Follow our WeChat subscription account for real-time updates and the latest in medical and biological research.


Business Email

E-mail: product@genelibs.com