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

The epidermal growth factor receptor family consists of four related tyrosi ne kinases: the epidermal growth factor receptor (EGF-R or ErbB), ErbB2, Er bB3, and ErbB4. These receptors are capable of extensive cross-activation u pon the binding of their ligands - the EGF family of peptides for EGF-R and the neuregulins for ErbB3 and ErbB4. Since EGF-R is expressed by prolifera ting cells in the central nervous system (CNS), including multipotent CNS s tem cells, we examined the expression of ErbB2, ErbB3 and ErbB4 in the germ inal epithelia of the developing rat brain using in situ hybridization. Erb B2 and ErbB4 mRNAs were widely distributed within the germinal zones as ear ly as E12. However, as development proceeded, ErbB2 mRNA was mainly present within the layers of cells immediately adjacent to the ventricular surface - the ventricular zone, while ErbB4 mRNA was predominantly expressed by su bventricular zone cells, in the regions where these specialized germinal ep ithelia were present. ErbB3 mRNA distribution within germinal epithelia was more restricted, primarily confined to the diencephalon and rostral midbra in. Cultured neurospheres, which contain CNS stem cells, expressed ErbB2, E rbB4 and, to a lesser extent, ErbB3 protein as demonstrated by Western blot analysis. This expression declined during following differentiation. Hereg ulin-beta 1, a neuregulin, had no effect on the proliferative capacity of n eurospheres. Overall, our results indicate that ErbB2, ErbB3 and ErbB4 may play important and distinct roles in the genesis of the CNS. However, our i n vitro data do not support a role for neuregulins in proliferation, per se , of CNS stem cells. Copyright (C) 2000 S. Karger AG, Basel.