SEPARATE CIS-ACTING ELEMENTS DETERMINE THE EXPRESSION OF MOUSE DBX GENE IN MULTIPLE SPATIAL DOMAINS OF THE CENTRAL-NERVOUS-SYSTEM

Dbx, a divergent homeobox gene, is expressed in a regionally restricte d pattern in the developing mouse central nervous system (CNS). In ord er to understand its spatial regulation, we have isolated a cis-regula tory region using a reporter gene analytical approach in transgenic mi ce. A 5.7 kb DNA fragment that contains the transcriptional start site of the Dbx gene is sufficient to direct the expression of the transge ne to various domains of the CNS in a temporally regulated fashion. Th e transgene expression can be detected between 9.5 and 15.5 days post coitum in embryos in the fore-, mid- and hindbrain and spinal cord in regions where the endogenous gene is expressed. Additionally, transgen e expression can also be detected in the oculomotor nerve (cranial ner ve III). The expression of the transgene closely resembles that of the Dbx gene with minor, but interesting differences. These results sugge st that major cis-acting elements reside within a 5.7 kb DNA fragment located 5' of the Dbx gene. Further deletion analysis shows that at le ast two independently regulated elements are present within this DNA f ragment: an element that directs expression to the brain and spinal co rd and a second element that directs expression to the oculomotor nerv e.