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Abnormal astrocyte development and neuronal death in mice lacking the epidermal growth factor receptor
Author(s) -
Kornblum Harley I.,
Hussain Raymond,
Wiesen Jane,
Miettinen Paivi,
Zurcher Shelley D.,
Chow Kit,
Derynck Rik,
Werb Zena
Publication year - 1998
Publication title -
journal of neuroscience research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.72
H-Index - 160
eISSN - 1097-4547
pISSN - 0360-4012
DOI - 10.1002/(sici)1097-4547(19980915)53:6<697::aid-jnr8>3.0.co;2-0
Subject(s) - biology , olfactory bulb , astrocyte , neuroscience , forebrain , progenitor cell , microbiology and biotechnology , central nervous system , stem cell
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 glia 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. J. Neurosci. Res. 53:697–717, 1998. © 1998 Wiley‐Liss, Inc.