Figure 1. Patterning functions of morphogens and ECM in mammary gland morphogenesis.

Upper panel: Confocal image of an engineered Y-shaped mammary epithelial branching tubule with (a) cells stained for actin (red) and nuclei (green). The computed spatial map of inhibitory diffusible morphogen TGF-β, produced by mammary epithelial cells (and shown in the form of a heatmap in (b) predicts that the local concentration of the inhibitor is highest at the point of trifurcation (where initiation of branching does not take place) and lowest at the distal ends of the tubules, where branching is allowed (c). Branching is determined by the interplay of the local tissue geometry and the spatial geometry of morphogen diffusion. (Adapted from Nelson et al 2006⁴⁴; Hayes et al, 2006¹²⁸)

Lower panel: Mouse mammary epithelial cells when cultured on top of laminin-111-rich ECM, develop into spheroid multicellular structures that are encased in basement membrane. These structures resemble in vivo mammary acini in size and shape. After four days, a lumen forms through epithelial cell death in the center. The lumen then fills up with milk, secreted by the peripheral epithelial cells. The lower left panel is a light microscope picture of an acinus from a section of a gland in vivo. The lower middle panel shows a low magnification transmission electron microscopic image of an acinus formed in culture. (Adapted from Barcellos-Hoff et al, 1989¹²⁹)