Expression of Dab2, a Tumor Suppressor, in the Human Fetal Hippocampus and Neocortex

Abstract

Dab2, first identified as a tumor suppressor in ovarian cancerous cells and tissues, is an adaptor protein involved in several signal transduction pathways. Our previous studies of mouse embryos have shown that Dab2 is expressed in the early developing central nervous system and that knockdown of the protein expression perturbs the normal development of the neural tube. In this study, we investigated Dab2 expression in the human fetal hippocampus and temporal, sensory, visual, motor and frontal cortices from 12 to 32 weeks of gestation with a specific immunohistochemical staining method. The hippocampus showed the strongest Dab2 expression among all the brain regions examined. Within the hippocampus, Dab2 expression was first detected at 12–14 weeks in all cellular layers with varying intensities, and the highest level of expression was observed in the pyramidal layer at 26–28 weeks. In the temporal cortex, Dab2 was also expressed in all cellular layers at 12–14 weeks, and its expression peaked at 18–20 weeks and then became weaker at 26–32 weeks. The expression pattern was different in the sensory cortex: the expression was the strongest at 12–14 weeks and then gradually reduced with age. In the visual cortex, Dab2 expression was mainly localized in the marginal zone, upper cortical plate and subcortical layers, whereas the motor and frontal cortices exhibited only low levels of Dab2 expression mostly in the subcortical layers. Our results demonstrated a specific spatiotemporal pattern of Dab2 expression in the human fetal hippocampus and neocortex, implicating roles of Dab2 in the early development of the human brain.