A 5.5-KB ENHANCER IS BOTH NECESSARY AND SUFFICIENT FOR REGULATION OF WNT-1 TRANSCRIPTION IN-VIVO

Wnt-1 encodes a secreted signaling molecule which is required for deve lopment of the midbrain and anterior hindbrain in the mouse. Wnt-1 exp ression is initiated early in the development of the central nervous s ystem in a region predicted to give rise to the midbrain. Later in dev elopment Wnt-1 expression is restricted to regions of the forebrain, m idbrain and spinal cord. Previous studies identified a 5.5-kb enhancer in the Wnt-1 locus which is sufficient to activate transcription of a reporter gene in a pattern very similar to that of the endogenous Wnt -1 gene. Here we have assessed if this enhancer is an important compon ent of the endogenous regulatory sequences of Wnt-1 by gene targeting and by testing if it is able to express Wnt-1 in a pattern which is su fficient to rescue the phenotype of loss of Wnt-1. Our results show th at the 5.5-kb enhancer is both necessary and sufficient for Wnt-1 expr ession in vivo. (C) 1997 Academic Press.