Specific developmental reductions in subventricular zone ErbB1 and ErbB4 mRNA in the human brain

Abstract

The primate postnatal subventricular zone (SVZ) lies under the ventrolateral borders of the lateral ventricles as a discrete region of cells with gliogenic and neurogenic capacity regulated by ErbB receptors. However, the specific role of each ErbB subtype in SVZ cell development remains unclear, particularly in the human brain. The postnatal spatial and temporal expression profile of ErbB subtypes in the human brain may provide valuable insight into their distinct functions in the SVZ following birth. Hence, we examined the expression profile of ErbB1, ErbB2, ErbB3 and ErbB4 mRNA in the SVZ of human postmortem brains from neonates, infants, toddlers, school age subjects, adolescents, young adults and adults using in situ hybridization. SVZ transcript levels of ErbB1 and ErbB4 were highest in neonates and diminished with age. SVZ ErbB4 mRNA quantities significantly decreased by >85% to almost undetectable levels after the first year of life, while SVZ ErbB1 transcript levels displayed more gradual reductions, stabilizing to approximately 30-40% of neonate levels after the age of 5 years. In the neonate and infant SVZ, ErbB4 mRNA was localized to cell clusters resembling migratory neuroblast aggregates whereas ErbB1 mRNA was expressed in cells along but not within these clusters. ErbB2 mRNA appeared to be constantly expressed in the human SVZ at all postnatal ages as opposed to ErbB3 transcripts, which were not detected in the human SVZ at any age following birth. These findings suggest that ErbB1 and ErbB4 may play more salient roles than ErbB2 and ErbB3 in mediating early postnatal neurodevelopmental events. In addition, ErbB1- and ErbB4-immunoreactive cells and fibers were extensive throughout the human infant SVZ, but did not appear to overlap with PSA-NCAM-immunopositive clusters. The restriction of robust SVZ ErbB4 expression to neonate and infant age groups may indicate that SVZ-derived ErbB4-dependent postnatal neuronal development is most extensive within a narrow time frame early after birth.