Figure 1.

Mutations to the ultraconserved SALL1 enhancer alter the spatial gene expression pattern. (a) Enhancer SALL1-D5 drives robust LacZ expression throughout the fore- and hindlimbs in embryonic day 11.5 (e11.5) mouse embryos in a pattern that is similar to limb expression of Sall1. (b) The SALL1-D5 enhancer is approximately 500 kb upstream of the transcriptional start site of human SALL1. To identify which sequences within the highly conserved 179 bp core of SALL1-D5 (grey bar) are crucial for limb expression, we engineered a series of substitution or deletion alleles, diagrammed here, and tested their effect on LacZ expression in e11.5 transgenic mouse embryos. To the right of each allele, the number of transgenic e11.5 embryos showing full, partial and no (neg) reporter gene expression in the limbs are indicated. The cartoons on the far right show the partial gene expression pattern observed for each allele. (c) Representative pictures of mouse e11.5 forelimbs showing full SALL1-D5 activity compared with partial activity patterns resulting from SALL1-D5 mutations. Partial patterns ranged from an overall reduction of SALL1-D5 activity throughout the limb to the restriction of activity to one side of the limb (anterior or posterior). A↔P: anterior-to-posterior axis, P↔D: proximal-to-distal axis.