ES2, A GENE DELETED IN DIGEORGE-SYNDROME, ENCODES A NUCLEAR-PROTEIN AND IS EXPRESSED DURING EARLY MOUSE DEVELOPMENT, WHERE IT SHARES AN EXPRESSION DOMAIN WITH A GOOSECOID-LIKE GENE

ES2 is a gene deleted in DiGeorge syndrome (DGS) and velocardiofacial syndrome (VCFS) which has homologs in species as distant as Caenorhabd itis elegans and Drosophila, The function of ES2 is unknown, and the p redicted protein sequence does not contain motifs which suggest a part icular role in the developmental defects present in DGS and VCFS, Here we show that the mouse homolog, Es2, is transcribed in two forms resu lting from the use of alternative polyadenylation signals, Structural analysis programs predict that the Es2-encoded peptide has a coiled-co il domain, and transfection experiments with an Es2-green fluorescent protein (GFP) fusion construct show that the peptide is recruited into the nucleus, Es2 is highly expressed during mouse embryogenesis from E7 onwards, In situ hybridization with an RNA probe revealed that the gene is widely expressed; however, relatively higher expression was de tected in the nervous system, with a particularly high area of express ion in a sub-region of the pens, The Es2 expression domain in the pens is shared with a Goosecoid-like gene (Gscl) which is located upstream of Es2,and raises the possibility that the two-genes share regulatory elements and/or interact in this region of the developing brain, This finding suggests that different genes in the deleted region may be fu nctionally related and might explain the occurrence of the characteris tic phenotype in patients with non-overlapping genetic lesions.