One of the best-studied aspects of epithelial-mesenchymal interaction during murine mammary development is the androgen-mediated destruction of the mammary bud in males. In male embryos, beginning on E14, the mammary mesenchyme condenses around the neck of the epithelial bud

The development of many epithelial organs depends on a series of sequential and reciprocal interactions between epithelial cells and adjacent mesenchymal or stromal cells (Thesleff et al., 1995; Birchmeier and Birchmeier, 1993). The mammary gland is an example of an organ where these epithelialmesenchymal interactions play a critical role, especially during embryonic development (Sakakura, 1987; Cunha, 1994; Robinson et al., 1999). In mice, mammary development commences with the formation of 5 pairs of epithelial buds located on the ventral surface of the embryo. Each bud begins as a localized thickening of the epidermis first noted on embryonic day 10 (E10, appearance of the vaginal plug = E0), and between E10 and E12-13 this initial placode invaginates into the underlying mesenchyme and the mammary epithelial cells organize themselves into a characteristic “light-bulb” shape (Sakakura, 1987; Robinson et al., 1999). Initially, the mammary mesenchyme is indistinguishable from the ventral dermal mesenchyme, but by the time the mammary epithelial bud is fully formed, it is invested by several layers of mesenchymal cells that are morphologically and functionally distinct from the surrounding dermal mesenchyme (Sakakura, 1987). Recombination experiments have documented that the mammary epithelium and mesenchyme contribute to the formation of each other during mammary bud development and, within the mature mammary bud (through E14-15), each compartment retains the capacity to induce fully the formation of the other (Propper and Gomot, 1967; Heuberger et al., 1982; Cunha et al., 1995). One of the best-studied aspects of epithelial-mesenchymal interaction during murine mammary development is the androgen-mediated destruction of the mammary bud in males. In male embryos, beginning on E14, the mammary mesenchyme condenses around the neck of the epithelial bud and disrupts the stalk connecting the mammary bud to the overlying epidermis (Turner and Gomez, 1933; Sakakura, 1987). In most strains of mice, the mammary epithelial remnant subsequently degenerates and no nipple is formed, explaining the lack of nipples and mammary glands in adult males (Sakakura, 1987). However, the degree to which the epithelial remnant is destroyed is variable and, in rats, while the stalk is destroyed, there is little degeneration of the remaining epithelium. Several studies have shown that this process occurs as a result of the secretion of androgens by the fetal testes, which act directly on the mammary mesenchyme to trigger its condensation (Raynaud and Frilley, 1947; Raynaud, 1949; Hoshino, 1965; Neuman et al., 1970; 3485 Development 126, 3485-3493 (1999) Printed in Great Britain © The Company of Biologists Limited 1999 DEV4185