Key stages of mammary gland development: molecular mechanisms involved in the formation of the embryonic mammary gland

Abstract

The development of the embryonic mammary gland involves communication between the epidermis and mesenchyme and is coordinated temporally and spatially by various signaling pathways. Although many more genes are likely to control mammary gland development, functional roles have been identified for Wnt, fibroblast growth factor, and parathyroid hormone-related protein signaling. This review describes what is known about the molecular mechanisms that regulate embryonic mammary gland development.

Figure 1

Embryonic mammary development. (a) Embryonic day (E)12.5. The epithelial cells have invaginated to form the initial bud, but the dense mammary mesenchyme has not yet formed. (b) Female bud at E14.5. The bud is fully formed. The epithelial cells are arrayed in a ball-on-stalk, or inverted bulb shape. The mesenchymal cells are arranged in four to five layers in a radial fashion around the epithelial cells. (c) Male bud at E14.5. Under the influence of testosterone, the mesenchymal cells condense around the stalk of the bud (arrowheads), constricting it until the connection with the surface epidermis is severed. After this occurs mammary mesenchyme cells and many epithelial cells undergo apoptosis. (d) Mammary sprout at E18.5. The epithelial bud has grown out from the mammary mesenchyme into the lower dermis, where it will enter the mammary fat pad and begin a period of active ductal branching morphogenesis. (e) A whole mount of the initial primary duct system from a 2-day-old mouse, the end-result of embryonic mammary morphogenesis. The arrowhead denotes the connection of the primary duct to the skin.

Figure 2

A model of mammary line specification and placode formation. Fibroblast growth factor (Fgf)10 from the ventrolateral portion of the somites acts in concert with Wnts expressed within the epidermis to specify the mammary line. This induces TBX3 expression, which in turn induces the expression of specific Wnts and Fgfs within the mammary line. These molecules act in an autocrine fashion and cooperate with other signaling pathways to form 10 pairs of placodes at specific locations along the original mammary line.