Developmental profile of ErbB receptors in murine central nervous system: implications for functional interactions

The ErbB family, ErbB1 (also known as the epidermal growth factor receptor EGFR), ErbB2, ErbB3, and ErbB4 comprise a group of receptor tyrosine kinases that interact with ligands from the epidermal growth factor (EGF) superfamily, subsequently dimerize, catalytically activate each other by cross-phosphorylation, and then stimulate various signaling pathways. To gain a better understanding of in vivo functions of ErbB receptors in the central nervous system, the current study examined their mRNA expression throughout development in the mouse brain via in situ hybridization. EGFR, ErbB2, and ErbB4 exhibited distinct but sometimes overlapping distributions in multiple cell types within germinal zones, cortex, striatum, and hippocampus in prenatal and postnatal development. In addition, a subpopulation of cells positive for ErbB4 mRNA in postnatal cortex and striatum coexpressed mRNA for either EGFR or GAD67, a marker for gamma-aminobutyric acid (GABA)ergic interneurons, suggesting that both ErbB4 and EGFR are coexpressed in GABAergic interneurons. In contrast, ErbB3 mRNA was not detected within the brain during development and only appeared in white matter tracts in adulthood. Together, these findings suggest that ErbB receptors might mediate multiple functions in central nervous system development, some of which may be initiated by EGFR/ErbB4 heterodimers in vivo.