In vertebrates, the hedgehog family of cell signaling proteins and associated downstream network components play an essential role in mediating tissue interactions during development and organogenesis. Loss-of-function or misexpression mutation of hedgehog network components can cause birth defects, skin cancer and other tumors. The mammary gland is a specialized skin derivative requiring epithelial-epithelial and epithelial-stromal tissue interactions similar to those required for development of other organs, where these interactions are often controlled by hedgehog signaling. We have investigated the role of the Patched-1 (Ptc1) hedgehog receptor gene in mammary development and neoplasia. Haploinsufficiency at the Ptc1 locus results in severe histological defects in ductal structure, and minor morphological changes in terminal end buds in heterozygous postpubescent virgin animals. Defects are mainly ductal hyperplasias and dysplasias characterized by multilayered ductal walls and dissociated cells impacting ductal lumens. This phenotype is 100% penetrant. Remarkably, defects are reverted during late pregnancy and lactation but return upon involution and gland remodeling. Whole mammary gland transplants into athymic mice demonstrates that the observed dysplasias reflect an intrisic developmental defect within the gland. However, Ptc1-induced epithelial dysplasias are not stable upon transplantation into a wild-type epithelium-free fat pad, suggesting stromal (or epithelial and stromal) function of Ptc1. Mammary expression of Ptc1 mRNA is both epithelial and stromal and is developmentally regulated. Phenotypic reversion correlates with developmentally regulated and enhanced expression of Indian hedgehog (Ihh) during pregnancy and lactation. Data demonstrate a critical mammary role for at least one component of the hedgehog signaling network and suggest that Ihh is the primary hedgehog gene active in the gland.

Abstract Macrophages regulate many developmental and pathological processes in both embryonic and adult tissues, and recent studies have shown a significant role in angiogenesis. Similarly, Wnt signaling is fundamental to tissue morphogenesis and also has a role in vascular development. In this review, we summarize recent advances in the field of macrophage-regulated angiogenesis, with a focus on the role of macrophage-derived Wnt ligands. We review data that provide both direct and indirect evidence for macrophage-derived Wnt regulation of physiologic and pathologic angiogenesis. Finally, we propose that Wnt signaling plays a central role in differentiation of tumor associated and wound infiltrating macrophages to a proangiogenic phenotype.

The spreading of Sn-3Ag-xBi solders on Fe-42Ni has been studied using a drop transfer setup. Initial spreading velocities as fast as ~0.5 m/s have been recorded. The results are consistent with a liquid front moving on a metastable, flat, unreacted substrate and can be described by using a modified molecular-kinetic model for which the rate controlling step is the movement of one atom from the liquid to the surface of the solid substrate. Although the phase diagram predicts the formation of two Fe-Sn intermetallics at the solder/substrate interface in samples heated at temperatures lower than 513oC, after spreading at 250oC only a thin FeSn reaction layer could be observed. Two interfacial layers (FeSn and FeSn2) were found after spreading at 450oC.