After puberty in mammals, the mammary gland undergoes substantial growth and differentiation. This is controlled by several hormones, with estrogen arguably being the most important. Mammary glands from mice that that are null for estrogen receptor α (ERα) or its downstream target amphiregulin (AREG) fail to display this post-pubertal growth and instead form rudimentary ducts. Here (p. 2018), Gilbert Smith and colleagues ask whether these growth-deficient mammary gland cells can induce the in vivo reprogramming of non-mammary cells (specifically testicular cells and neural stem cells) into a mammary cell fate in the same way as wild-type mammary cells are known to do. They find that AREG−/− cells can mediate the redirection of non-mammary cells into differentiated mammary epithelial cells; AREG−/− cells and non-mammary cells co-injected into fat pads in virgin mice form an alveolar outgrowth that is capable, upon pregnancy, of milk secretion. ERα−/− cells, however, only show a limited ability to induce such reprogramming, with chimeras of ERα−/− and non-mammary cells failing to grow. This demonstrates that AREG is indispensable for post-pubertal ductal growth in the mouse but is not required for alveolar development and function, whereas ERα is essential for both processes. The results presented further suggest that estrogen signals through as-yet-unidentified genes to induce mammary development, and thus open up a new avenue for future research.
