Skip to main content
Log in

Roles of transforming growth factor-α and related molecules in the nervous system

  • Published:
Molecular Neurobiology Aims and scope Submit manuscript

Abstract

The epidermal growth factor (EGF) family of polypeptides is regulators for tissue development and repair, and is characterized by the fact that their mature forms are proteolytically derived from their integral membrane precursors. This article reviews roles of the prominent members of the EGF family (EGF, transforming growth factor-alpha [TGF-α] and heparin-binding EGF [HB-EGF]) and the related neuregulin family in the nerve system. These polypeptides, produced by neurons and glial cells, play an important role in the development of the nervous system, stimulating proliferation, migration, and differentiation of neuronal, glial, and Schwann precursor cells. These peptides are also neurotrophic, enhancing survival and inhibiting apoptosis of post-mitotic neurons, probably acting directly through receptors on neurons, or indirectly via stimulating glial proliferation and glial synthesis of other molecules such as neurotrophic factors. TGF-α, EGF, and neuregulins are involved in mediating glial-neuronal and axonal-glial interactions, regulating nerve injury responses, and participating in injury-associated astrocytic gliosis, brain tumors, and other disorders of the nerve system. Although the collective roles of the EGF family (as well as those of the neuregulins) are shown to be essential for the nervous system, redundancy may exist among members of the EGF family.

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

Access this article

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

Instant access to the full article PDF.

Similar content being viewed by others

References

  • Abe K. and Saito H. (1992) Protective effect of epidermal growth factor on glutamate neurotoxicity in cultured cerebellar neurons.Neurosci. Res. 14, 117–123.

    PubMed  CAS  Google Scholar 

  • Alexi T., Venero J. L., and Hefti F. (1997) Protective effects of neurotrophin-4/5 and transforming growth factor-alpha on striatal neuronal phenotypic degeneration after excitotoxic lesioning with quinolinic acid.Neuroscience 78, 73–86.

    PubMed  CAS  Google Scholar 

  • Anton E. S., Marchionni M. A., Lee K. F., and Rakic P. (1997) Role of GGF/neuregulin signaling in interactions between migrating neurons and radial glia in the developing cerebral cortex.Development 124, 3501–3510.

    PubMed  CAS  Google Scholar 

  • Baek S. Y. and Kim S. U. (1998) Proliferation of human Schwann cells induced by neu differentiation factor isoforms.Dev. Neurosci. 20, 512–517.

    PubMed  CAS  Google Scholar 

  • Bargmann C. I., Hung M.-C., and Weinberg R. A. (1986) The neu oncogene encodes an epidermal growth factor receptor-related protein.Nature 319, 226–230.

    PubMed  CAS  Google Scholar 

  • Barnard J. A., Beauchamp R. D., Russell W. E., Dubois R. N., and Coffey R. J. (1995) Epidermal growth factor-related peptides and their relevance to gastrointestinal pathophysiology.Gastroenterology 108, 564–580.

    PubMed  CAS  Google Scholar 

  • Birecree E., King L. E., and Naney L. B. (1991) Epidermal growth factor and its receptor in the developing human nervous system.Dev. Brain Res. 60, 145–154.

    CAS  Google Scholar 

  • Blum M. (1998) A null mutation in TGF-alpha leads to a reduction in midbrain dopaminergic neurons in the substantia nigra.Nat. Neurosci. 1, 374–377.

    PubMed  CAS  Google Scholar 

  • Boniece I. R. and Wagner J. A. (1993) Growth factors protect PC12 cells against ischemia by a mechanism that is independent of PKA, PKC, and protein synthesis.J. Neurosci. 13, 4220–4228.

    PubMed  CAS  Google Scholar 

  • Britsch S., Li L., Kirchhoff S., Theuring F., Brinkmann V., Birchmeier C., and Riethmacher D. (1998) The ErbB2 and ErbB3 receptors and their ligand, neuregulin-1, are essential for development of the sympathetic nervous system.Genes. Dev. 12, 1825–1836.

    PubMed  CAS  Google Scholar 

  • Burrows R. C., Wancio D., Levitt P., and Lillien L. (1997) Response diversit and the timing of progenitor cell maturation are regulated by developmental changes in EGFR expression in the cortex.Neuron 19, 251–267.

    PubMed  CAS  Google Scholar 

  • Carraway K. L., Weber J. L., Unger M. J., Ledesma J., Yu N., Gassmann M., and Lai C. (1997) Neuregulin-2, a new ligand of ErbB3/ErbB4-receptor tyrosine kinase.Nature 387, 512–516.

    PubMed  CAS  Google Scholar 

  • Carroll S. L., Miller M. L., Frohnert P. W., Kim S. S., and Corbett J. A. (1997) Expression of neuregulins and their putative receptors, ErbB2 and ErbB3, is induced during Wallerian degeneration.J. Neurosci. 17, 1642–1659.

    PubMed  CAS  Google Scholar 

  • Casper D., Mytilineou C., and Blum M. (1991) EGF enhances the survival of dopamine neurons in rat embryonic mesencephalon primary cell culture.J. Neurosci. Res. 30, 372–381.

    PubMed  CAS  Google Scholar 

  • Chalazonitis A., Kessler J. A., Twardzik D. R., and Morrison R. S. (1992) Transforming growth factor alpha, but not epidermal growth factor, promotes the survival of sensory neurons in vitro.J. Neurosci. 12, 583–594.

    PubMed  CAS  Google Scholar 

  • Chang H., Riese D. J., Gilbert W., Stern D. F., and McMahan U. J. (1997) Ligands for ErbB-family receptors encoded by a neuregulin-like gene.Nature 387, 509–512.

    PubMed  CAS  Google Scholar 

  • Chiasson B. J., Tropepe V., Morshead C. M., and van der Kooy D. (1999) Adult mammalian forebrain ependymal and subependymal cell demonstrate proliferative potential, but only subependymal cell have neural stem cell characteristics.J. Neurosci. 19, 4462–4471.

    PubMed  CAS  Google Scholar 

  • Chicoine M. R., Madsen C. L., and Silbergeld D. L. (1995) Modification of human glioma locomotion in vitro by cytokines EGF, bFGF, PDGFbb, NGF, and TNF alpha.Neurosurgery 36, 1165–1170.

    PubMed  CAS  Google Scholar 

  • Ciccolini F. and Svendsen C. N. (1998) Fibroblast growth factor 2 (FGF-2) promotes acquisition of epidermal growth factor (EGF) responsiveness in mouse striatal precursor cells: identification of neural precursors responding to both EGF and FGF-2.J. Neurosci. 18, 7869–7880.

    PubMed  CAS  Google Scholar 

  • Condorelli D. F., Kaczmarek L., Nicoletti F., Arcidiacono A., Dell'Albani P., Ingrao F., et al. (1989) Induction of protooncogene fos by extracellular signals in primary glial cell cultures.J. Neurosci. Res. 23, 234–239.

    PubMed  CAS  Google Scholar 

  • Cosgaya J. M. and Aranda A. (1996) Ras- and Raf-mediated regulation of transforming growth factor beta 1 gene expression by ligands of tyrosine kinase receptors in PC12 cells.Oncogene 12, 2651–2660.

    PubMed  CAS  Google Scholar 

  • Craig C. G., Tropepe V., Morshead C. M., Reynolds B. A., Weiss S., and van der Kooy D. (1996) In vivo growth factor expansion of endogenous subependymal neural precursor cell populations in the adult mouse brain.J. Neurosci. 16, 2649–2658.

    PubMed  CAS  Google Scholar 

  • Creedon D. J. and Tuttle J. B. (1997) Synergistic increase in nerve growth factor secretion by cultured vascular smooth muscle cells treated with injury-related growth factors.J. Neurosci. Res. 47, 277–286.

    PubMed  CAS  Google Scholar 

  • Derynck R. (1988) Transforming growth factor-α.Cell 54, 593–595.

    PubMed  CAS  Google Scholar 

  • Derynck R. (1992) The physiology of transforming growth factor-α.Advanc. Cancer Res. 58, 27–52.

    CAS  Google Scholar 

  • Dong Z., Brennan A., Liu N., Yarden Y., Lefkowitz G., Mirsky R., and Jessen K. R. (1995) Neu differentiation factor is a neuron-glial signal and regulates survival, proliferation, and maturation of rat Schwann cell precursors.Neuron 15, 585–596.

    PubMed  CAS  Google Scholar 

  • Engebraaten O., Bjerkvig R., Pedersen P. H., and Laerum O. D. (1993) Effects of EGF, bFGF, NGF and PDGF(bb) on cell proliferative, migratory and invasive capacities of human brain-tumour biopsies in vitro.Int. J. Cancer 53, 209–214.

    PubMed  CAS  Google Scholar 

  • Engele J. and Schilling K. (1996) Growth factor-induced c-fos expression defines distinct subsets of midbrain dopaminergic neurons.Neuroscience 73, 397–406.

    PubMed  CAS  Google Scholar 

  • Erickson S. L., O'Shea K. S., Ghaboosi N., Loverro L., Frantz G., Bauer M., et al. (1997) ErbB3 is required for normal cerebellar and cardiac development: a comparison with ErbB2- and heregulin-deficient mice.Development 124, 4999–5011.

    PubMed  CAS  Google Scholar 

  • Faber Elman A., Solomon A., Abraham J. A., Marikovsky M., and Schwartz M. (1996) Involvement of wound-associated factors in rat brain astrocyte migratory response to axonal injury: in vitro simulation.J. Clin. Invest. 97, 162–171.

    PubMed  CAS  Google Scholar 

  • Fallon J. H., Annis C. M., Gentry L. E., Twardzik D. R., and Loughlin S. E. (1990) Localization of cells containing transforming growth factor-α precursor immunoreactivity in the basal ganglia of the adult rat brain.Growth Factors 2, 241–250.

    PubMed  CAS  Google Scholar 

  • Falls D. L., Rosen K. M., Corfas G., Lane W. S., and Fischbach G. D. (1993) ARIA, a protein that stimulates acetylcholine receptor synthesis, is a member of the neu ligand family.Cell 72, 801–815.

    PubMed  CAS  Google Scholar 

  • Ferrair G., Toffano G., and Skaper S. D. (1991) Epidermal growth factor exerts neuronotrophic effects on dopaminergic and GABAergic CNS neurons: comparison with basic fibroblast growth factor.J. Neurosci. Res. 30, 493–497.

    Google Scholar 

  • Ferrer I., Alcantara S., Ballabriga J., Olive M., Blanco R., Rivera, R., et al. (1996) Transforming growth factor-alpha (TGF-alpha) and epidermal growth factor-receptor (EGF-R) immunoreactivity in normal and pathologic brain.Prog. Neurobiol. 49, 99–123.

    PubMed  CAS  Google Scholar 

  • Ferrer I., Blanco R., Carulla M., Condom M., Alcantara S., Olive M., and Planas A. (1995) Transforming growth factor-alpha immunoreactivity in the developing and adult brain.Neuroscience 66, 189–199.

    PubMed  CAS  Google Scholar 

  • Ferri R. T. and Levitt P. (1995) Regulation of regional differences in the differentiation of cerebral cortical neurons by EGF family-matrix interactions.Development 121, 1151–1160.

    PubMed  CAS  Google Scholar 

  • Gangarosa L. M., Dempsey P. J., Damstrup L., Barnard J. A., and Coffey R. J. (1996) Transforming growth factor-α.Bailliere's Clin. Gastroenterol. 10, 49–63.

    CAS  Google Scholar 

  • Gassmann M. and Lemke G. (1997) Neuregulins and neuregulin receptors in neural development.Curr. Opin Neurobiol. 7, 87–92.

    PubMed  CAS  Google Scholar 

  • Gassmann M., Casagranda F., Orioli D., Simon H., Lai C., Klein R., and Lemke G. (1995) Aberrant neural and cardiac development in mice lacking the ErbB4 neruegulin receptor.Nature 378, 390–394.

    PubMed  CAS  Google Scholar 

  • Goldman C. K., Kim J., Wong W. L., King V., Brock T., and Gillespie G. Y. (1993) Epidermal growth factor stimulates vascular endothelial growth factor production by human malignant glioma cells: a model of glioblastoma multiforme pathophysiology.Mol. Biol. Cell 4, 121–133.

    PubMed  CAS  Google Scholar 

  • Goumnerova L. C. (1996) Growth factor receptors and medulloblastoma.J. Neurooncol. 29, 85–89.

    PubMed  CAS  Google Scholar 

  • Graus Porta D., Beerli R. R., Daly J. M., and Hynes N. E. (1997) ErbB-2, the preferred heterodimerization partner of all ErbB receptors, is a mediator of lateral signaling.EMBO J. 16, 1647–1655.

    PubMed  CAS  Google Scholar 

  • Grinspan J. B., Marchionni M. A., Reeves M., Coulaloglou M., and Scherer S. S. (1996) Axonal interactions regulate Schwann cell apoptosis in developing peripheral nerve: neuregulin receptors and the role of neuregulins.J. Neurosci. 16, 6107–6118.

    PubMed  CAS  Google Scholar 

  • Han V. K. M., Smith A., Myint W., Nygard K., and Bradshaw S. (1992) Mitogenic activity of epidermal growth factor on newborn rat astroglia: interaction with insulin-like growth factors.Endocrinology 131, 1134–1142.

    PubMed  CAS  Google Scholar 

  • Harari D., Tzahar E., Romano J., Shelly M., Pierce J. H., Andrews G. C., and Yarden Y. (1999) Neuregulin-4: a novel growth factor that acts through the ErbB-4 receptor tyrosine kinase.Oncogene 18, 2681–2689.

    PubMed  CAS  Google Scholar 

  • Homes W. E., Sliwkowski M. X., Akita R. W., Henzel W. J., Lee J., Park J. W., et al. (1992) Identification of heregulin, a specific activator of p185erbB2.Science 256, 1205–1210.

    Google Scholar 

  • Huang S. S., Lokeshwar V. B., and Huang J. S. (1988) Modulation of the epidermal growth factor receptor by brain-derived growth factor in Swiss mouse 3T3 cells.J. Cell Biochem. 36, 209–221.

    PubMed  CAS  Google Scholar 

  • Huerta J. J., Diaz Trelles R., Naves F. J., Llamosas M. M., del Valle M. E., and Vega J. A. (1996) Epidermal growth factor receptor in adult human dorsal root ganglia.Anat. Embryol. Berl. 194, 253–257.

    PubMed  CAS  Google Scholar 

  • Iwasaki K., Isaacs K. R., and Jacobowitz D. M. (1998) Brain-derived neurotrophic factor stimulates neurite outgrowth in a calretinin-enriched neuronal culture system.Intl. J. Dev. Neurosci. 16, 135–145.

    CAS  Google Scholar 

  • Jensen R. L. (1998) Growth factor-mediated angiogenesis in the malignant progression of glial tumors: a review.Surg. Neurol. 49, 189–195.

    PubMed  CAS  Google Scholar 

  • Jonakait G. M., Luskin M. B., and Ni L. (1998) Transforming growth factor-alpha expands progenitor cells of the basal forebrain, but does not promote cholinergic differentiation.J. Neurobiol. 37, 405–412.

    PubMed  CAS  Google Scholar 

  • Junier M.-P., Hill D. F., Costa M. E., Felder S. E., and Ojeda S. R. (1993) Hypothalamic lesions that induce female precocious puberty activate glial expression of the epidermal growth factor receptor gene: differential regulation of alternatively spliced transcripts.J. Neurosci. 13, 703–713.

    PubMed  CAS  Google Scholar 

  • Junier M.-P., Ma Y. J., Costa M. E., Hoffman G., Hill D. F., and Ojeda S. R. (1991) Transforming growth factor alpha contributes to the mechanism by which hypothalamic injury induces precocious puberty.Proc. Natl. Acad. Sci. USA 88, 9743–9747.

    PubMed  CAS  Google Scholar 

  • Junier M. P., Coulpier M., Le Forestier N., Cadusseau J., Suzuki F., Peschanski M., and Dreyfus P. A. (1994) Transforming growth factor alpha (TGF alpha) expression in degenerating motoneurons of the murine mutant wobbler: a neuronal signal for astrogliosis?J. Neurosci. 14, 4206–4216.

    PubMed  CAS  Google Scholar 

  • Junier M. P., Legendre P., Esguerra C. V., Tinel M., Coulpier M., Dreyfus P. A., and Bahr M. (1998) Regulation of growth factor gene expression in degenerating motoneurons of the murine mutant wobbler: a cellular patch-sampling/RT-PCR study.Mol. Cell Neurosci. 12, 168–177.

    PubMed  CAS  Google Scholar 

  • Justicia C. and Planas A. M. (1999) Transforming growth factor-alpha acting at the epidermal growth factor receptor reduces infarct volume after permanent cerebral artery occlusion in rats.J. Cereb. Blood Flow Metab. 19, 128–132.

    PubMed  CAS  Google Scholar 

  • Kamiguchi H., Yoshida K., Sagoh M., Sasaki H., Inaba M., Wakamoto H., et al., (1995) Release of ciliary neurotrophic factor from cultured astrocytes and its modulation by cytokines.Neurochem. Res. 20, 1187–1193.

    PubMed  CAS  Google Scholar 

  • Kaser M. R., Lakshmanan J., and Fisher D. A. (1992) Comparison between epidermal growth factor, transforming growth factor-alpha and EGF receptor levels in regions of adult rat brain.Brain Res. Mol. Brain Res. 16, 316–322.

    PubMed  CAS  Google Scholar 

  • Kawahara N., Mishima K., Higashiyama S., Taniguchi N., Tamura A., and Kirino T. (1999) The gene for heparin-binding epidermal growth factor-like growth factor is stress-inducible: its role in cerebral ischemia.J. Cereb. Blood. Flow. Metab. 19, 307–320.

    PubMed  CAS  Google Scholar 

  • Kenigsberg R. L. and Mazzoni I. E. (1995) Identification of glial cell types involved in mediating epidermal growth factor's effects on septal cholinergic neurons.J. Neurosci. Res. 41, 734–744.

    PubMed  CAS  Google Scholar 

  • Kleihues P., Soylemezoglu F., Schauble B., Scheithauer B. W., and Burger P. C. (1995) Histopathology, classification, and grading of gliomas.Glia 15, 211–221.

    PubMed  CAS  Google Scholar 

  • Kornblum H. I., Hussain R. J., Bronstein J. M., Gall C. M., Lee D. C., and Seroogy K. B. (1997) Prenatal ontogeny of the epidermal growth factor receptor and its ligand, transforming growth factor alpha, in the rat brain.J. Comp. Neurol. 380, 243–261.

    PubMed  CAS  Google Scholar 

  • Kornblum H. I., Hussain R., Wiesen J., Miettinen P., Zurcher S. D., Chow K., et al. (1998) Abnormal astrocyte development and neuronal death in mice lacking the epidermal growth factor receptor.J. Neurosci. Res. 53, 697–717.

    PubMed  CAS  Google Scholar 

  • Kornblum H. I., Raymon H. K., Morrison R. S., Cavanaugh K. P., Badshaw R. A., and Leslie F. M. (1990) Epidermal growth factor and basic fibroblast growth factor: effects on an overlapping population of neocortical neurons in vitro.Brain Res. 535, 255–263.

    PubMed  CAS  Google Scholar 

  • Kornblum H. I., Yanni D. S., Easterday M. C., and Seroogy K. B. (2000) Expression of the EGF receptor family members ErbB2, ErbB3, and ErbB4 in germinal zones of the developing brain and in neurosphere cultures containing CNS stem cells.Dev. Neurosci. 22, 16–24.

    PubMed  CAS  Google Scholar 

  • Kornblum H. I., Zurcher S. D., Werb Z., Derynck R., and Seroogy K. B. (1999) Multiple trophic actions of heparin-binding epidermal growth factor (HB-EGF) in the central nervous system.Eur. J. Neurosci. 11, 3236–3246.

    PubMed  CAS  Google Scholar 

  • Kraus M. H., Issing W., Miki T., Popescu N. C., and Aaronson S. A. (1989) Isolation and characterization of ERBB3, a third member of the ERBB/epidermal growth factor receptor family: evidence for overexpression in a subset of human mammary tumors.Proc. Natl. Acad. Sci. USA 86, 9193–9197.

    PubMed  CAS  Google Scholar 

  • Krieglstein K. and Unsicker K. (1997) Protein from chromaffin granules promotes survival of mesencephalic dopaminergic neurons by an EGF-receptor ligand-mediated mechanism.J. Neurosci. Res. 48, 18–30.

    PubMed  CAS  Google Scholar 

  • Kudlow J. E., Leung A. W., Kobrin M. S., Paterson A. J., and Asa S. L. (1989) Transforming growth factoralpha in the mammalian brain. Immunohistochemical detection in neurons and characterization of its mRNA.J. Biol. Chem. 264, 3880–3883.

    PubMed  CAS  Google Scholar 

  • Kuhn H. G., Winkler J., Kempermann G., Thal L. J., and Gage F. H. (1997) Epidermal growth factor and fibroblast growth factor-2 have different effects on neural progenitors in the adult rat brain.J. Neurosci. 17, 5820–5829.

    PubMed  CAS  Google Scholar 

  • Lauder J. M. and Liu J. (1994) Glial heterogeneity and developing neurotransmitter systems.Perspect. Dev. Neurobiol. 2, 239–250.

    PubMed  CAS  Google Scholar 

  • Lazar L. M. and Blum M. (1992) Regional distribution and development expression of epidermal growth factor and transforming growth factoralpha mRNA in mouse brain by a quantitative nuclease protection assay.J. Neurosci. 12, 1688–1697.

    PubMed  CAS  Google Scholar 

  • Lazarovici P., Dickens G., Kuzuya H., and Guroff G. (1987) Long-term, heterologous down-regulation of the epidermal growth factor receptor in PC12 cells by nerve growth factor.J. Cell Biol. 104, 1611–1621.

    PubMed  CAS  Google Scholar 

  • Lee D. C., Fenton S. E., Berkowitz E. A., and Hissong M. A. (1995a) Transforming growth factor α: expression, regulation, and biological activities.Pharmacol. Rev 47, 51–85.

    PubMed  CAS  Google Scholar 

  • Lee D. C., Rose T. M., Webb N. R., and Todaro G. J. (1985) Cloning and sequence analysis of a cDNA for rat transforming growth factor-α.Nature 313, 489–491.

    PubMed  CAS  Google Scholar 

  • Lee K., Simon H., Chen H., Bates B., Hung M., and Hauser C. (1995b) Requirement for neuregulin receptor erbB2 in neural and cardiac development.Nature 387, 394–398.

    Google Scholar 

  • Lemke G. (1996) Neuregulins in development.Mol. Cell. Neurol. 7, 247–262.

    CAS  Google Scholar 

  • Leon S. P., Zhu J., and Black P. M. (1994) Genetic aberrations in human brain tumors.Neurosurgery 34, 708–722.

    PubMed  CAS  Google Scholar 

  • Leutz A. and Schachner M. (1981) Epidermal growth factor stimulates DNA synthesis of astrocytes for primary cerebellar cultures.Cell Tissue Res. 220, 393–404.

    PubMed  CAS  Google Scholar 

  • Lewin G. R. and Barde Y. A. (1996) Physiology of the neurotrophins.Annu. Rev. Neurosci. 19, 289–317.

    PubMed  CAS  Google Scholar 

  • Lillien L. (1995) Changes in retinal cell fate induced by overexpression of EGF receptor.Nature 377, 158–162.

    PubMed  CAS  Google Scholar 

  • Lindholm D., Castren E., Kiefer R., Zafra F., and Thoenen H. (1992) Transforming growth factorbeta 1 in the rat brain: increase after injury and inhibition of astrocyte proliferation.J. Cell Biol. 117, 395–400.

    PubMed  CAS  Google Scholar 

  • Lindholm D., Heumann R., Meyer M., and Thoenen H. (1987) Interleukin-1 regulates synthesis of nerve growth factor in non-neuronal cells of rat sciatic nerve.Nature 330, 658–659.

    PubMed  CAS  Google Scholar 

  • Lisovoski F., Blot S., Lacombe C., Bellier J. P., Dreyfus P. A., and Junier M. P. (1997) Transforming growth factor alpha expression as a response of murine motor neurons to axonal injury and mutation-induced degeneration.J. Neuropathol. Exp. Neurol. 56, 459–471.

    PubMed  CAS  Google Scholar 

  • Logan A., Oliver J. J., and Berry M. (1994) Growth factors in CNS repair and regeneration.Prog. Growth Factor Res. 5, 379–405.

    PubMed  CAS  Google Scholar 

  • Loo D. T., Bradford S., Helmrich A., and Barnes D. W. (1998) Bcl-2 inhibits cell death of serum-free mouse embryo cells caused by epidermal growth factor deprivation.Cell Biol. Toxico. 14, 375–382.

    CAS  Google Scholar 

  • Lu N., Black I. B., and DiCicco Bloom E. (1996) A paradigm for distinguishing the roles of mitogenesis and trophism in neuronal precursor proliferation.Brain Res. Dev. Brain Res. 94, 31–36.

    PubMed  CAS  Google Scholar 

  • Lu X. and Richardson P. M. (1991) Inflammation near the nerve cell body enhances axonal regeneration.J. Neurosci. 11, 972–978.

    PubMed  CAS  Google Scholar 

  • Luetteke N. C., Qiu T. H., Fenton S. E., Troyer K. L., Riedel R. F., Chang A., and Lee D. C. (1999) Targeted inactivation of the EGF and amphiregulin genes reveals distinct roles for EGF receptor ligands in mouse mammary gland development.Development 126, 2739–2750.

    PubMed  CAS  Google Scholar 

  • Luetteke N. C., Qiu T. H., Peiffer R. L., Oliver P., Smithies O., and Lee D. C. (1993) TGF-α deficiency results in hair follicle and eye abnormalities in targeted and waved-1 mice.Cell 73, 263–278.

    PubMed  CAS  Google Scholar 

  • Lund Johansen M., Bjerkvig R., Humphrey P. A., Bigner S. H., Bigner D. D., and Laerum O. D. (1990) Effect of epidermal growth factor on glioma cell growth, migration, and invasion in vitro.Cancer Res. 50, 6039–6044.

    PubMed  CAS  Google Scholar 

  • Ma Y. J., Berg von der Emde K., Rage F., Wetsel W. C., and Ojeda S. R. (1997) Hypothalamic astrocytes respond to transforming gorwth factor-alpha with the secretion of neuroactive substances that stimulate the release of luteininzing hormone-releasing hormone.Endocrinology 138, 19–25.

    PubMed  CAS  Google Scholar 

  • Ma Y. J., Junier M.-P., Costa M. E., and Ojeda S. R. (1992) Transforming growth factor-α gene expression in the hypothalamus is developmentally regulated and linked to sexual maturation.Neuron 9, 657–670.

    PubMed  CAS  Google Scholar 

  • Mann G. B., Fowler K. J., Gabriel A., Nice E. C., Williams R. L., and Dunn A. R. (1993) Mice with a null mutation of the TGF-α gene have abnormal skin architecture, wavy hair, and curly whiskers and often develop corneal inflammation.Cell 73, 249–261.

    PubMed  CAS  Google Scholar 

  • marchetti B. (1996) The LHRH-astroglial network of signals as a model to study neuroimmune interactions: assessment of messenger systems and transduction mechanisms at cellular and molecular levels.Neuroimmunomodulation 3, 1–27.

    PubMed  CAS  Google Scholar 

  • Marchionni M. A., Goodearl A. D., Chen M. S., Berminham-McDonogh O., Kirk C., Hendricks et al. (1993) Glial growth factors are alternatively spliced erbB2 ligands expressed in the nervous system.Nature 362, 312–318.

    PubMed  CAS  Google Scholar 

  • Mazzoni I. E. and Kenigsberg R. L. (1994) Localization and characterization of epidermal growth-factor receptors in the developing rat medical septal area in culture.Brain Res. 656, 115–126.

    PubMed  CAS  Google Scholar 

  • Mazzoni I. E. and Kenigsberg R. L. (1996) Transforming growth factor alpha differentially affects GABAergic and cholinergic neurons in rat medial septal cell cultures.Brain Res. 707, 88–99.

    PubMed  CAS  Google Scholar 

  • Mehler M. F. and Gokhan S. (1999) Postnatal cerebral cortical multipotent progenitors: regulatory mechanisms and potential role in the development of novel neural regenerative strategies.Brain Pathol. 9, 515–526.

    PubMed  CAS  Google Scholar 

  • Meyer D. and Birchmeier C. (1994) Distinct isoforms of neurgulin are expressed in mesenchymal and neuronal cells during mouse development.Proc. Natl. Acad. Sci. USA 91, 1064–1068.

    PubMed  CAS  Google Scholar 

  • Meyer D. and Birchmeier C. (1995) Multiple essential functions of neuregulin in development.Nature 378, 386–390.

    PubMed  CAS  Google Scholar 

  • Mirsky R. and Jessen K. R. (1999) The neurobiology of Schwann cells.Brain Pathol. 9, 293–311.

    PubMed  CAS  Google Scholar 

  • Mirsky R., Stewart H. J., Tabernero A., Bradke F., Brennan A., Dong Z., and Jessen K. R. (1996) Development and differentiation of Schwann cells.Rev. Neurol. 152, 308–313.

    PubMed  CAS  Google Scholar 

  • Mishima K., Asai A., Sugiyama A., Miyagi Y., Kitanaka C., Kagaya S., et al. (1996) Increased expression of schwannoma-derived growth factor mRNA in rat tumor cells: involvement of SDGF in the growth promotion of rat gliomas.Intl. J. Cancer 66, 352–357.

    CAS  Google Scholar 

  • Morrison R. S., Kornblum H. I., Leslie F. M., and Bradshaw R. A. (1987) Trophic stimulation of cultured neurons from neonatal rat brain by epidermal growth factor.Science 238, 72–75.

    PubMed  CAS  Google Scholar 

  • Nakagaito Y., Satoh M., Kuno H., Iwama T., Takeuchi M., Hakura A., and Yoshida T. (1998) Establishment of an epidermal growth factor-dependent, multipotent neural precursor cell line.In Vitro Cell Dev. Biol. Anim. 34, 585–592.

    PubMed  CAS  Google Scholar 

  • Nakagawa T., Sasahara M., Hayase Y., Haneda M., Yasuda H., Kikkawa R., et al. (1998) Neuronal and glial expression of heparin-binding EGF-like growth factor in central nervous system of prenatal and early-postnatal rat.Brain Res. Dev. Brain Res. 108, 263–272.

    PubMed  CAS  Google Scholar 

  • Nieto-Sampedro M. (1988) Astrocyte mitogen inhibitor related to epidermal growth factor receptor.Science 240, 1784–1786.

    PubMed  CAS  Google Scholar 

  • Ohgaki H., Schauble B., zur Hausen A., von Ammon K., and Kleihues P. (1995) Genetic alterations associated with the evolution and progression of astrocytic brain tumors.Virchows Arch. 427, 113–118.

    PubMed  CAS  Google Scholar 

  • Ojeda S. R. and Ma Y. J. (1998) Epidermal growth factor tyrosine kinase receptors and the neuroendocrine control of mammalian puberty.Mol. Cell Endocrinol. 140, 101–106.

    PubMed  CAS  Google Scholar 

  • Opanashuk L. A., Mark R. J., Porter J., Damm D., Mattson M. P., and Seroogy K. B. (1999) Heparin-binding epidermal growth factor-like growth factor in hippocampus: modulation of expression by seizures and anti-excitotoxic action.J. Neurosci. 19, 133–146.

    PubMed  CAS  Google Scholar 

  • Oude Weernink P. A., Verheul E., Kerkhof E., van Veelen C. W., and Rijksen G. (1996) Inhibitors of protein tyrosine phosphorylation reduce the proliferation of two human glioma cell lines.Neurosurgery 38, 108–113.

    PubMed  CAS  Google Scholar 

  • Peng H., Wen T. C., Tanaka J., Maeda N., Matsuda S., Desaki J., et al. (1998) Epidermal growth factor protects neuronal cells in vivo and in vitro against transient forebrain ischemia- and free radical-induced injuries.J. Cereb. Blood Flow Metab. 18, 349–360.

    PubMed  CAS  Google Scholar 

  • Plowman G. D., Culouscou J.-M., Whitney G. S., Green J. M., Carlton G. W., Foy L., et al. (1993) Ligand-specific activation of HER4/p180erbB4, a fourth member of the epidermal growth factor receptor family.Proc. Natl. Acad. Sci. USA 90, 1746–1750.

    PubMed  CAS  Google Scholar 

  • Prigent S. A. and Lemoine N. R. (1992) The type 1 (EGFR-related) family of growth factor receptors and their ligands.Prog. Growth Factor Res. 4, 1–24.

    PubMed  CAS  Google Scholar 

  • Rabchevsky A. G., Weinitz J. M., Coulpier M., Fages C., Tinel M., and Junier M. P. (1998) A role for transforming growth factor alpha as an inducer of astrogliosis.J. Neurosci. 18, 10,541–10,552.

    CAS  Google Scholar 

  • Rao M. S. (1999) Multipotent and restricted precursors in the central nervous system.Anat. Rec. 257, 137–148.

    PubMed  CAS  Google Scholar 

  • Reifenberger G., Reifenberger J., Bilzer T., Wechsler W., and Collins V. P. (1995) Coexpression of transforming growth factor-alpha and epidermal growth factor receptor in capillary hemangioblastomas of the central nervous system.Am. J. Pathol. 147, 245–250.

    PubMed  CAS  Google Scholar 

  • Riese D. J. and Stern D. F. (1998) Specificity within the EGF family/ErbB receptor family signaling network.Bioessays 20, 41–48.

    PubMed  Google Scholar 

  • Riethmacher D., Sonnenberg-Riethmacher E., Brinkmann V., Yamaai T., Lewin G. R., and Birchmeier C. (1997) Severe neuropathies in mice with targeted mutations in the ErbB3 receptor.Nature 389, 725–729.

    PubMed  CAS  Google Scholar 

  • Rosenberg A. and Noble E. P. (1989) EGF-induced neuritogenesis and correlated synthesis of plasma membrane gangliosides in cultured embryonic chick CNS neurons.J. Neurosci. Res. 24, 531–536.

    PubMed  CAS  Google Scholar 

  • Sagar S. M., Edwara's R. H., and Sharp F. R. (1991) Epidermal growth factor and transforming growth factor alpha induce c-fos gene expression in retinal Muller cells in vivo.J. Neurosci. Res. 29, 549–559.

    PubMed  CAS  Google Scholar 

  • Santa-Olalla J. and Covarrubias L. (1995) Epidermal growth factor (EGF), transforming growth factor-alpha (TGF-alpha), and basic fibroblast growth factor (bFGF) differentially influence neural precursor cells of mouse embryonic mesencephalon.J. Neurosci. Res. 42, 172–183.

    PubMed  CAS  Google Scholar 

  • Santa-Olalla J. and Covarrubias L. (1999) Basic fibroblast growth factor promotes epidermal growth factor responsiveness and survival of mesencephalic neural precursor cells.J. Neurobiol. 40, 14–27.

    PubMed  CAS  Google Scholar 

  • Satoh T., Enokido Y., Kubo T., Yamada M., and Hatanaka H. (1998) Oxygen toxicity induces apoptosis in neuronal cells.Cell Mol. Neurobiol. 18, 649–666.

    PubMed  CAS  Google Scholar 

  • Saxena A. and Ali I. U. (1992) Increased expression of genes from growth factor signaling pathways in glioblastoma cell lines.Oncogene 7, 243–247.

    PubMed  CAS  Google Scholar 

  • Seroogy K. B., Gall C. M., Lee, D. C., and Kornblum H. I. (1995) Proliferative zones of postnatal rat brain express epidermal growth factor receptor mRNA.Brain Res. 670, 157–164.

    PubMed  CAS  Google Scholar 

  • Seroogy K. B., Han V. K., and Lee D. C. (1991) Regional expression of transforming growth factor-alpha mRNA in the rat central nervous system.Neurosci. Lett. 125, 241–245.

    PubMed  CAS  Google Scholar 

  • Seroogy K. B., Lundgren K. H., Lee D. C., Guthrie K. M., and Gall C. M. (1993) Cellular localization of transforming growth factor-alpha mRNA in rat forebrain.J. Neurochem. 60, 1777–1782.

    PubMed  CAS  Google Scholar 

  • Seroogy K. B., Numan S., Gall C. M., Lee D. C., and Kornblum H. I. (1994) Expression of EGF receptor mRNA in rat nigrostriatal system.Neuroreport 6, 105–108.

    PubMed  CAS  Google Scholar 

  • Shetty A. K. and Turner D. A. (1998) In vitro survival and differentiation of neurons derived from epidermal growth factor-responsive postnatal hippocampal stem cells: inducing effects of brain-derived neurotrophic factor.J. Neurobiol. 35, 395–425.

    PubMed  CAS  Google Scholar 

  • Sibilia M., Steinbach J. P., Stingl L., Aguzzi A., and Wagner E. F. (1998) A strain-independent postnatal neruodegeneration in mice lacking the EGF receptor.EMBO J. 17, 719–731.

    PubMed  CAS  Google Scholar 

  • Snider W. D. (1994) Functions of the neurotrophins during nervous system development: what the knockouts are teaching us.Cell 77, 627,628.

    PubMed  Google Scholar 

  • Spranger M., Lindholm D., Bandtlow C., Heumann R., Gnahn H., Naher-Noe M., and Thoenen H. (1990) Regulation of nerve growth factor (NGF) synthesis in the rat central nervous system: comparison between the effects of interleukin-1 and various growth factors in astrocyte cultures and in vivo.Eur. J. Neurosci. 2, 69–76.

    PubMed  Google Scholar 

  • Steiner H., Blum M., Kitai S. T., and Fedi P. (1999) Differential expression of ErbB3 and ErbB4 neuregulin receptors in dopamine neurons and forebrain areas of the adult rat.Exp. Neurol. 159, 494–503.

    PubMed  CAS  Google Scholar 

  • Stephenson J. L. and Byers M. R. (1995) GFAP immunoreactivity in trigeminal ganglion satellite cells after tooth injury in rats.Exp. Neurol. 131, 11–22.

    PubMed  CAS  Google Scholar 

  • Sundaresan S., Roberts P. E., King K. L., Sliwkowski M. X., and Mather J. P. (1998) Biological response to ErbB ligands in nontransformed cell lines correlates with a specific pattern of receptor expression.Endocrinology 139, 4756–4764.

    PubMed  CAS  Google Scholar 

  • Svendsen C. N., Caldwell M. A., Shen J., ter Borg M. G., Rosser A. E., Tyers P., et al. (1997) Longterm survival of human central nervous system progenitor cells transplanted into a rat model of Parkinson's disease.Exp. Neurol. 148, 135–146.

    PubMed  CAS  Google Scholar 

  • Syroid D. E., Maycox P. R., Burrola P. G., Liu N., Wen D., Lee K. F., et al. (1996) Cell death in the Schwann cell lineage and its regulation by neuregulin.Proc. Natl. Acad. Sci. USA 93, 9229–9234.

    PubMed  CAS  Google Scholar 

  • Tang P., Steck P. A., and Yung W. K. (1997) The autocrine loop of TGF-alpha/EGFR and brain tumors.J. Neuroonocol. 35, 303–314.

    CAS  Google Scholar 

  • Threadgill D. W., Dlugosz A. A., Hansen L. A., Tennenbaum T., Lichti U., Yee D., et al. Mourton T., Herrup K. (1995) Targeted disruption of mouse EGF receptor: effect of genetic background on mutant phenotype.Science 269, 230–234.

    PubMed  CAS  Google Scholar 

  • Toma J. G., Pareek S., Barker P., Mathew T. C., Murphy R. A., Acheson A., and Miller F. D. (1992) Spatiotemporal increases in epidermal growth factor receptors following peripheral nerve injury.J. Neurosci. 12, 2504–2515.

    PubMed  CAS  Google Scholar 

  • Topp K. S., Faddis B. T., and Vijayan V. K. (1989) Trauma-induced proliferation of astrocytes in the brains of young and aged rats.Glia 2, 201–211.

    PubMed  CAS  Google Scholar 

  • Tropepe V., Craig C. G., Morshead C. M., and van der Kooy D. (1997) Transforming growth factor-alpha null and senescent mice show decreased neural progenitor cell proliferation in the fore-brain subependyma.J. Neurosci. 17, 7850–7859.

    PubMed  CAS  Google Scholar 

  • Tropepe V., Sibilia M., Ciruna B. G., Rossant J., Wagner E. F., and van der Kooy D. (1999) Distinct neural stem cells proliferate in response to EGF and FGF in the developing mouse telencephalon.Dev. Biol. 208, 166–188.

    PubMed  CAS  Google Scholar 

  • Tucker M. S., Eves E. M., Wainer B. H., and Rosner M. R. (1993) Activation of mitogen-activated protein kinase by epidermal growth factor in hippocampal neurons and neuronal cell lines.J. Neurochem. 61, 1376–1387.

    PubMed  CAS  Google Scholar 

  • Tucker M. S., Khan I., Fuchs Young R., Price S., Steininger T. L., et al. (1993) Localization of immunoreactive epidermal growth factor receptor in neonatal and adult rat hippocampus.Brain Res. 631, 65–71.

    PubMed  CAS  Google Scholar 

  • Tzahar E., Waterman H., Chen X., Levkowitz G., Karunagaran D., Lavi S., et al. (1996) A hierarchical network of interreceptor interactions determines signal transduction by Neu differentiation factor/neuregulin and epidermal growth factor.Mol. Cell Biol. 16, 5276–5287.

    PubMed  CAS  Google Scholar 

  • Vartanian T., Fischbach G., and Miller R. (1999) Failure of spinal cord oligodendrocyte development in mice lacking neuregulin.Proc. Natl. Acad. Sci. USA 96, 731–735.

    PubMed  CAS  Google Scholar 

  • Vartanian T., Goodearl A., Viehover A., and Fischbach G. (1997) Axonal neuregulin signals cells of the oligodendrocyte lineage through activation of HER4 and Schwann cells through HER2 and HER3.J. Cell Biol. 137, 211–220.

    PubMed  CAS  Google Scholar 

  • Vega J. A., Vazquez E., Naves F. J., Calzada B., del Valle M. E., and Represa J. J. (1994) Expression of epidermal growth factor receptor (EGFr) immunoreactivity in human cutaneous nerves and sensory corpuscles.Anat. Rec. 240, 125–130.

    PubMed  CAS  Google Scholar 

  • Ventrella L. L. (1993) Effect of intracerebroventricular infusion of epidermal growth factor in rats hemitransected in the nigro-striatal pathway.J. Neurosurg. Sci. 37, 1–8.

    PubMed  CAS  Google Scholar 

  • Verdi J. M., Groves A. K., Farinas I., Jones K., Marchionni M. A., Reichardt L. F., and Anderson D. J. (1996) A reciprocal cell-cell interaction mediated by NT-3 and neuregulins controls the early survival and development of sympathetic neuroblasts.Neuron 16, 515–527.

    PubMed  CAS  Google Scholar 

  • von Deimling A., Louis D. N., and Wiestler O. D. (1995) Molecular pathways in the formation of gliomas.Glia 15, 328–338.

    Google Scholar 

  • Wang, S. L., Shiverick K. T., Ogilvie S., Dunn W. A., and Raizada M. K. (1989) Characterization of epidermal growth factor receptors in astrocytic glial and neuronal cells in primary culture.Endocrinology 124, 240–247.

    PubMed  CAS  Google Scholar 

  • Weickert C. S. and Blum M. (1995) Striatal TGF-alpha: postnatal developmental expression and evidence for a role in the proliferation of subependymal cells.Brain Res. Dev. Brain Res. 86, 203–216.

    PubMed  CAS  Google Scholar 

  • Weiss S., Dunne C., Hewson J., Wohl C., Wheatley M., Peterson A. C., and Reynolds B. A. (1996a) Multipotent CNS stem cells are present in the adult mammalian spinal cord and ventricular neuroaxis.J. Neurosci. 16, 7599–7609.

    PubMed  CAS  Google Scholar 

  • Weiss S., Reynolds B. A., Vescovi A. L., Moreshead C., Craig C. G., and van der Kooy D. (1996b) Is there a neural stem cell in the mammalian forebrain?Trends Neurosci. 19, 387–393.

    PubMed  CAS  Google Scholar 

  • Werner M. H., Nanney L. B., Stoscheck C. M., and King L. E. (1988) Localization of immunoreactive epidermal growth factor receptors in human nervous system.J. Histochem. Cytochem. 36, 81–86.

    PubMed  CAS  Google Scholar 

  • Whittemore S. R., Morassutti D. J., Walters W. M., Liu R. H., and Magnuson D. S. (1999) Mitogen and substrate differentially affect the lineage restriction of adult rat subventricular zone neural precursor cell populations.Exp. Cell Res. 252, 75–95.

    PubMed  CAS  Google Scholar 

  • Wilcox J. N. and Derynck R. (1988) Localization of cells synthesizing transforming growth factor-alpha mRNA in the mouse brain.J. Neurosci. 8, 1901–1904.

    PubMed  CAS  Google Scholar 

  • Winkler C., Fricker R. A., Gates M. A., Olsson M., Hammang J. P., Carpenter M. K., and Bjorklund A. (1998) Incorporation and glial differentiation of mouse EGF-responsive neural progenitor cells after transplantation into the embryonic rat brain.Mol. Cell Neurosci. 11, 99–116.

    PubMed  CAS  Google Scholar 

  • Wu C. F. and Howard B. D. (1995) K252a-potentiation of EGF-induced neurite outgrowth from PC12 cells is not mimicked or blocked by other protein kinase activators or inhibitors.Brain Res. Dev. Brain Res. 86, 217–226.

    PubMed  CAS  Google Scholar 

  • Xian C. J. and Zhou X.-F. (1999) Neuronal-glial differential expression of TGF-α and its receptor in the dorsal root ganglia in response to sciatic nerve lesion.Exp. Neurol. 157, 317–326.

    PubMed  CAS  Google Scholar 

  • Yamada M., Enokido Y., Ikeuchi T., and Hatanaka H. (1995) Epidermal growth factor prevents oxygen-triggered apoptosis and induces sustained signaling in cultured rat cerebral cortical neurons.Eur. J. Neurosci. 7, 2130–2138.

    PubMed  CAS  Google Scholar 

  • Yamada M., Ikeuchi T., Aimoto S., and Hatanaka H. (1996a) PC12h-R cell, a subclone of PC12 cells, shows EGF-induced neuronal differentiation and sustained signaling.J. Neurosci. Res. 43, 355–364.

    PubMed  CAS  Google Scholar 

  • Yamada M., Ikeuchi T., Aimoto S., and Hatanaka H. (1996b) EGF-induced sustained tyrosine phosphorylation and decreased rate of down-regulation of EGF receptor in PC12h-R cells which show neuronal differentiation in response to EGF.Neurochem. Res. 21, 815–822.

    PubMed  CAS  Google Scholar 

  • Yamada M., Ikeuchi T., and Hatanaka H. (1997) The neurotrophic action and signaling of epidermal growth factor.Prog. Neurobiol. 51, 19–37.

    PubMed  CAS  Google Scholar 

  • Yamazaki H., Ohba Y., Tamaoki N., and Shibuya M. (1990) A deletion mutation within the ligand binding domain is responsible for activation of epidermal growth factor receptor gene in human brain tumors.Jpn. J. Cancer Res. 81, 773–779.

    PubMed  CAS  Google Scholar 

  • Yasui W., Ji Z. Q., Kuniyasu H., Ayhan A., Yokozaki H., Ito H., and Tahara E. (1992) Expression of transforming growth factor alpha in human tissues: immunohistochemical study and northern blot analysis.Virchows Arch. A Pathol. Anat. Histopathol. 421, 513–519.

    PubMed  CAS  Google Scholar 

  • Yoshida K. and Gage F. H. (1992) Cooperative regulation of nerve growth factor synthesis and secretion in fibroblasts and astrocytes by fibroblast growth factor and other cytokines.Brain Res. 569, 14–25.

    PubMed  CAS  Google Scholar 

  • Yoshida T., Satoh M., Nakagaito Y., Kuno H., and Takeuchi M. (1993) Cytokines affecting survival and differentiation of an astrocyte progenitor cell line.Brain Res. Dev. Brain Res. 76, 147–150.

    PubMed  CAS  Google Scholar 

  • Zhang D., Sliwkowski M. X., Mark M., Frantz G., Akita R., Sun Y., et al. (1997) Neuregulin-3 (NRG3): a novel neural tissue-enriched protein that binds and activates ErbB4.Proc. Natl. Acad. Sci. USA 94, 9562–9567.

    PubMed  CAS  Google Scholar 

  • Zhang M. B., Woo D. D., and Howard B. D. (1990) Transforming growth factor alpha and a PC12-derived growth factor induce neurites in PC12 cells and enhance the survival of embryonic brain neurons.Cell Regul. 1, 511–521.

    PubMed  CAS  Google Scholar 

  • Zhou X.-F., McLachlan E. M., and Rush R. A. (1996) Differential expression of p75 nerve growth factor receptor by glia and neurons in the dorsal root ganglia following peripheral nerve injury.J. Neurosci. 16, 2901–2911.

    PubMed  CAS  Google Scholar 

  • Zorick T S. and Lemke G. (1996) Schwann cell differentiation.Curr. Opin. Cell Biol. 8, 870–876.

    PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Cory J. Xian.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Xian, C.J., Zhou, XF. Roles of transforming growth factor-α and related molecules in the nervous system. Mol Neurobiol 20, 157–183 (1999). https://doi.org/10.1007/BF02742440

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF02742440

Index Entries

Navigation