ALK1 is involved in multiple stages of lymphatic development. (A) Analysis of vascular and lymphatic development in P8 pups when ALK1Fc treatment is started when the honeycomb pattern is being established (10 mg/kg, P3 and P5). Lymphatic development is visualized by LYVE1 (green) staining in the tail dermis, whereas vascular development is visualized by isolectin-B4 (green) staining of the retina. Scale bar represents 500 μm (retina) and 250 μm (tail). (B) Analysis of lymphatic development in P12 pups when ALK1 treatment is started when the honeycomb structure is fully established (10 mg/kg, P8 and P10). Lymphatic development is visualized by LYVE1 (green) staining in the tail dermis. Scale bar represents 250 μm. (C) High-magnification images demonstrate the remodeling process that occurs from P8 to P12 and the “ringed” structures that fail to be remodeled in ALK1Fc-treated pups.