ABNORMAL ASTROCYTE DEVELOPMENT AND NEURONAL DEATH IN MICE LACKING THEEPIDERMAL GROWTH-FACTOR RECEPTOR

Stimulation of the epidermal growth factor receptor (EGF-R) produces n umerous effects on central nervous system (CNS) cells in vitro includi ng neuronal survival and differentiation, astrocyte proliferation and the proliferation of multipotent progenitors. However, the in vivo rol e of EGF-R is less well understood, In the present study, we demonstra te that EGF-R null mice generated on a 129Sv/J Swiss Black background undergo focal but massive degeneration the olfactory bulb, piriform co rtex, 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 z ones in early postnatal ages, At or just prior to the onset of the deg eneration, however, there was an increase in GFAP expression in these areas. The brains of EGF-R -/- animals were smaller but cytoarchitectu rally normal at birth and neuronal populations appeared to be intact, including striatal GABAergic and midbrain dopaminergic neurons which h ave previously been shown to express EGF-R, Multipotent progenitors an d 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, (C) 1998 W iley-Liss, Inc.