Profiling of genes expressed by PTEN haploinsufficient neural precursor cells

PTEN is a lipid phosphatase, and PTEN mutations are associated with gliomas, macrocephaly, and mental deficiencies. We have used PTEN +/− and PTEN +/+ mice to prepare subventricular zone (SVZ) precursor cells. Using DNA microarrays, we compared the expression profiles of PTEN +/+ and PTEN +/− cells and identified 91 differentially expressed genes in PTEN +/− precursor cells. Many of the PTEN-regulated genes are involved with signaling, cytoskeleton, extracellular matrix, metabolism, and transcription factors. Some of these changes are likely mediated by the transcription factor, HIF-1. We confirmed a subset of these changes by real-time PCR. In addition, we examined protein levels for two of the PTEN-up-regulated genes, vascular endothelial growth factor (VEGF) and doublecortin (DCX). PTEN haploinsufficiency increases immunostaining for VEGF for both cultured precursor cells and sections of the SVZ. PTEN haploinsufficiency shifted most of the DCX-positive cells from the SVZ to the olfactory bulb. These observations indicate that even a small decrease in PTEN levels results in substantial changes in gene expression and precursor cell function. [Copyright &y& Elsevier]