GOOSECOID-LIKE, A GENE DELETED IN DIGEORGE AND VELOCARDIOFACIAL SYNDROMES, RECOGNIZES DNA WITH A BICOID-LIKE SPECIFICITY AND IS EXPRESSED IN THE DEVELOPING MOUSE-BRAIN

The vast majority of patients with DiGeorge syndrome (DGS) and velocar diofacial syndrome (VCFS) have deletions of chromosomal region 22q11.2 , These patients exhibit broad and variable phenotypes that include co notruncal cardiac defects, hypocalcemia, palatal and facial anomalies and developmental delay. Most of these abnormalities are thought to be due to defects in neural crest cell migration or differentiation. We have identified a homeobox-containing gene, Goosecoid-like (GSCL), tha t is in the region within 22q11 that is deleted most consistently in p atients with DGS/VCFS, The GSCL gene is expressed in a limited number of adult tissues as well as in early human development, and is a membe r of a family of homeobox genes in vertebrates that includes Goosecoid and GSX. In this report, we present functional studies of the GSCL pr otein and determine the expression pattern of the GSCL gene in mouse e mbryos, We demonstrate that GSCL exhibits DNA sequence-specific recogn ition of sites bound by the Drosophila anterior morphogen, Bicoid, Sev eral of these sites (TAATCCC) were found in the 5' upstream region of the GSCL gene itself, and we present evidence suggesting that GSCL mig ht regulate its own transcription, In situ hybridization revealed that the mouse ortholog of GSCL, Gscl, is expressed in the brain starting as early as embryonic day 9.5, and expression continues in adults. Thi s expression pattern is consistent with GSCL having either an indirect role in the development of neural crest-derived structures or a direc t role in a subset of the phenotype observed in DGS/VCFS, such as lear ning disorders or psychiatric disease.