Cis-acting regulatory sequences governing Wnt-1 expression in the developing mouse CNS

Abstract

The protooncogene Wnt-1 encodes a short-range signal which is first expressed in, and appears to demarcate, the presumptive midbrain. Absence of Wnt-1 expression leads to the loss of this region of the brain. By the end of neural tube closure, expression of Wnt-1 extends down much of the dorsal midline of the central nervous system (CNS). Expression is exclusively limited to the CNS at this and later stages. We have investigated the regulation of Wnt-1 during mouse development. Analysis of the embryonic expression of Wnt-1-lacZ reporter constructs spanning nearly 30 kb of the Wnt-1 locus identified a 5.5 kb cis-acting 3′ enhancer element which confers correct temporal and spatial expression on the lacZ gene. Interestingly embryos express Wnt-1-lacZ transgenes in migrating neural crest cells which are derived from the dorsal CNS. Ectopic expression of the Wnt-1-lacZ transgenes may result from perdurance of β-galactosidase activity in migrating neural crest cells originating from a Wnt-1-expressing region of the dorsal CNS. Alternatively, ectopic expression may arise from transient de novo activation of the transgenes in this cell population. These results are a first step towards addressing how regional cell signaling is established in the mammalian CNS. In addition, transgene expression provides a new tool for the analysis of neural crest development in normal and mutant mouse embryos.