Stage-dependent regulation of mammary ductal branching by heparan sulfate and HGF-cMet signaling

►Ductal branching depends upon HS based on conditional deletion of Ext1. ►Secondary branching and end bud bifurcation depends on sulfation catalyzed by Hs2st. ►Secondary branching not terminal end bud bifurcation depends on HS-binding HGF. ►Hs2st and c-Met play important, but potentially independent roles in secondary and ductal-side branching. ►Distinct branching stages have differing dependencies on HS and its sulfation.