Regulation of mammary gland branching morphogenesis by the extracellular matrix and its remodeling enzymes.

A considerable body of research indicates that mammary gland branching morphogenesis is dependent, in part, on the extracellular matrix (ECM), ECM-receptors, such as integrins and other ECM receptors, and ECM-degrading enzymes, including matrix metalloproteinases (MMPs) and their inhibitors, tissue inhibitors of metalloproteinases (TIMPs). There is some evidence that these ECM cues affect one or more of the following processes: cell survival, polarity, proliferation, differentiation, adhesion, and migration. Both three-dimensional culture models and genetic manipulations of the mouse mammary gland have been used to study the signaling pathways that affect these processes. However, the precise mechanisms of ECM-directed mammary morphogenesis are not well understood. Mammary morphogenesis involves epithelial 'invasion' of adipose tissue, a process akin to invasion by breast cancer cells, although the former is a highly regulated developmental process. How these morphogenic pathways are integrated in the normal gland and how they become dysregulated and subverted in the progression of breast cancer also remain largely unanswered questions

Immunohistochemical localisation of TRA-1-60, TRA-1-81, GCTM-2 and podocalyxin in the developing baboon kidney

The baboon is an ideal animal model to study human kidney development. The aim of the current study was to use immunohistochemistry to localise the antigens TRA-1-60, TRA-1-81, GCTM-2 and podocalyxin in the developing baboon kidney where nephrogenesis was still on-going and in kidneys where nephrogenesis was complete. Fixed kidney sections from baboons delivered at 125, 140, 175 and 185 days gestation (term = 185 days) were immuno-labelled with antibodies directed against TRA- 1-60, TRA-1-81, GCTM-2 and podocalyxin. In kidneys with on-going nephrogenesis (125 and 140 days gestation), TRA-1-60, TRA-1-81 and GCTM-2 were speciWcally localised to the apical plasma membrane of the epithelium of the ureteric ampullae and the collecting ducts, while podocalyxin immunostaining was not detected. In kidneys where nephrogenesis was complete (175 and 185 days gestation) localisation of these markers was again very speciWcally localised to the collecting ducts. In conclusion, although further experimentation is required to conWrm the identity of the speciWc cell types marked by these antibodies, this study provides new insight into the distribution of commonly utilised stem cell antibodies in the developing baboon kidney