The mouse homeodomain protein OTX2 regulates NCAM promoter activity

The homeodomain transcription factor OTX2 is involved in defining regional identities in developing rostral brain. It appears to participate in morpho genetic processes leading to the formation of boundaries and substrates for early axon growth, processes which are in the end largely based on site-sp ecific expression of cell adhesion molecules. Here, we present evidence tha t a candidate target of OTX2 is the gene encoding the neural cell adhesion molecule, NCAM. When Otx2 is transfected into NIH3T3 cells, NCAM protein ex pression is upregulated. Moreover, while mock-transfected cells display onl y the 140 kDa-isoform of NCAM, Otx2 transfected cells express also the two other major isoforms (NCAM-120 and -180), in agreement with the presence of the corresponding transcripts in Northern blots. In addition, transient ex pression of Otx2 in COS7 cells is able to dramatically enhance the transcri ptional activity of the NCAM promoter. Taken together, our results argue fo r a regulation of NCAM expression by OTX2. (C) 1999 Published by Elsevier S cience B.V. All rights reserved.