Murine homolog of SALL1 is essential for ureteric bud invasion in kidney development

SALL1 is a mammalian homolog of the Drosophila region-specific homeotic gen e spalt (sal); heterozygous mutations in SALL1 in humans lead to Townes-Bro cks syndrome. We have isolated a mouse homolog of SALL1 (Sall1) and found t hat mice deficient in Sall1 die in the perinatal period and that kidney age nesis or severe dysgenesis are present. Sall1 is expressed in the metanephr ic mesenchyme surrounding ureteric bud; homozygous deletion of Sall1 result s in an incomplete ureteric bud outgrowth, a failure of tubule formation in the mesenchyme and an apoptosis of the mesenchyme. This phenotype is likel y to be primarily caused by the absence of the inductive signal from the ur eter, as the Sall1-deficient mesenchyme is competent with respect to epithe lial. differentiation. Sall1 is therefore essential for ureteric bud invasi on, the initial key step for metanephros development.