CONTROL OF VASCULAR CELL-ADHESION MOLECULE-1 GENE PROMOTER ACTIVITY DURING NEURAL DIFFERENTIATION

Here we demonstrate that vascular cell adhesion molecule-1 (VCAM-1) is expressed in the developing central nervous system on neuroepithelial cells, which are the precursors of neurons and glia. As these cells d ifferentiate, VCAM-1 is restricted to a subset of the glial population . An understanding of mechanisms responsible for this restricted patte rn could provide insights into how lineage-specific gene expression is maintained during neural differentiation. As a model of neural differ entiation, we turned to the P19 embryonic carcinoma cell line, which i n response to retinoic acid will differentiate along a neural pathway. We show that VCAM-1 expression on the differentiating P19 cells resem bles that in the central nervous system. Transfection of VCAM-1 gene p romoter constructs into P19 cells revealed that the VCAM-1 gene is con trolled sequentially by negative and positive elements during differen tiation. We present evidence that early during differentiation, POU pr oteins block VCAM-1 gene activity; however, later in differentiation c oincident with the appearance of VCAM-1 the pattern of POU proteins ch anges and the VCAM-1 gene promoter is activated. This activation is me diated through the NF kappa B/rel complex p50/p65, which forms during P19 cell differentiation.