Abnormal astrocyte development and neuronal death in mice lacking the epidermal growth factor receptor

Harley I. Kornblum, Raymond Hussain, Jane Wiesen, Paivi Miettinen, Shelley D. Zurcher, Kit Chow, Rik Derynck, Zena Werb

Research output: Contribution to journalArticlepeer-review

118 Scopus citations


Stimulation of the epidermal growth factor receptor (EGF-R) produces numerous effects on central nervous system (CNS) cells in vitro including neuronal survival and differentiation, astrocyte proliferation and the proliferation of multipotent progenitors. However, the in vivo role of EGF-R is less well understood. In the present study, we demonstrate that EGF-R null mice generated on a 129Sv/J Swiss Black background undergo focal but massive degeneration the olfactory bulb, piriform cortex, neocortex, and thalamus between postnatal days 5 and 8 which is due, at least in part, to apoptosis. Some of the neuronal populations that degenerate do not normally express EGF- R, indicating an indirect mechanism of neuronal death. There were also delays in GFAP expression within the gila limitans and within structures outside the germinal zones in early postnatal ages. At or just prior to the onset of the degeneration, however, there was an increase in GFAP expression in these areas. The brains of EGF-R -/- animals were smaller but cytoarchitecturally normal at birth and neuronal populations appeared to be intact, including striatal GABAergic and midbrain dopaminergic neurons which have previously been shown to express EGF-R. Multipotent progenitors and astrocytes derived from EGF-R -/- mice were capable of proliferating in response to FGF-2. These data demonstrate that EGF-R expression is critical for the maintenance of large portions of the postnatal mouse forebrain as well as the normal development of astrocytes.

Original languageEnglish (US)
Pages (from-to)697-717
Number of pages21
JournalJournal of Neuroscience Research
Issue number6
StatePublished - Sep 15 1998
Externally publishedYes


  • Apoptosis
  • Astrocyte
  • Brain
  • Epidermal growth factor receptor
  • Fibroblast growth factor
  • Ischemia
  • Knockout mouse
  • Neuron
  • Progenitor cell
  • Stem cell

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience


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