Lens epithelium-derived growth factor (LEDGF/p75) expression in fetal and adult human brain

Abstract

Lens epithelium-derived growth factor (LEDGF/p75) is a novel transcription co-activator that is critically involved in lens epithelial cell gene regulation and stress responses. Recent evidence indicates that LEDGF/p75 may play an important role in lens epithelial to fibre cell terminal differentiation. Since the lens and the brain are both ectodermally derived organs generated from epithelioid progenitor cells, we hypothesize that LEDGF/p75 is expressed and subserving similar functions in both organs. To investigate this hypothesis, we studied LEDGF/p75 expression and localization in the human brain. We detected LEDGF/p75-specific RT-PCR reaction products in both fetal and adult human brain. LEDGF/p75 mRNA expression in the brain exhibited differential developmental and regional specificity. LEDGF/p75 transcript was markedly elevated in fetal as compared to adult brain. In the adult brain, LEDGF/p75 mRNA expression was substantial in the subventricular zone (SVZ), scant in hippocampus, and undetectable elsewhere. To study LEDGF/p75 protein expression and localization, we developed and purified a new anti-LEDGF/p75 polyclonal antibody directed against a unique C-terminal region of LEDGF/p75. Western blot analysis of fetal and adult human brain revealed a ∼75 kDa protein that demonstrated developmental and regional specificity similar to that detected by RT-PCR analysis. LEDGF/p75 protein expression was high in fetal brain and in the adult SVZ. Immunohistochemical studies of human fetal brain showed prominent LEDGF/p75-immunoreactive cells in the germinal neuroepithelium and cortical plate regions. Analysis of adult and aged human brain revealed LEDGF/p75-immunoreactive cell enrichment in the SVZ adjacent to the ventral region of the lateral ventricle at the level of the anterior commissure, a region implicated in adult neurogenesis. We utilised a primary mixed cortical cell culture system to identify LEDGF/p75 in neurons, but not astrocytes. Neuronal LEDGF/p75 exhibited a predominantly perinuclear distribution pattern. These data demonstrate that LEDGF/p75 is expressed in discrete regions and cell types within the fetal and adult human brain. Moreover, the developmental and regional expression patterns of LEDGF/p75 suggest that this transcriptional co-activator may be involved in neuroepithelial stem cell differentiation and neurogenesis.