Prenatal Mammary Gland Development in the Mouse: Research Models and Techniques for Its Study from Past to Present

Mammary gland development starts during prenatal life, when at designated positions along the ventrolateral boundary of the embryonic or fetal trunk, surface ectodermal cells coalesce to form primordia for mammary glands, instead of differentiating into epidermis. With the wealth of genetically engineered mice available as research models, our understanding of the prenatal phase of mammary development has recently greatly advanced. This understanding includes the recognition of molecular and mechanistic parallels between prenatal and postnatal mammary morphogenesis and even tumorigenesis, much of which can moreover be extrapolated to human. This makes the murine embryonic mammary gland a useful model for a myriad of questions pertaining to normal and pathological breast development. Hence, unless indicated otherwise, this review describes embryonic mammary gland development in mouse only, and lists mouse models that have been examined for defects in embryonic mammary development. Techniques that originated in the field of developmental biology, such as explant culture and tissue recombination, were adapted specifically to research on the embryonic mammary gland. Detailed protocols for these techniques have recently been published elsewhere. This review describes how the development and adaptation of these techniques moved the field forward from insights on (comparative) morphogenesis of the embryonic mammary gland to the understanding of tissue and molecular interactions and their regulation of morphogenesis and functional development of the embryonic mammary gland. It is here furthermore illustrated how generic molecular biology and biochemistry techniques can be combined with these older, developmental biology techniques, to address relevant research questions. As such, this review should provide a solid starting point for those wishing to familiarize themselves with this fascinating and important subdomain of mammary gland biology, and guide them in designing a relevant research strategy.