Embryonic Mammary Gland Development

Abstract

Abstract Mammary glands are derived from the ectoderm and are a defining feature of mammals. The number of glands that develop along the ‘mammary lines’ on either side of the ventral trunk depends on the mammalian species. The mesoderm specifies the position in which glands develop. Positional information is encoded by transcription factors and transmitted to overlying ectoderm by signalling molecules. Determination of the mammary epithelium arises from induction of transcription factors and signalling molecules. Signals from the mammary epithelium induce the underlying mesoderm to form the mammary mesenchyme required for further development. The gland initiates as a discrete placode which sinks into the mesoderm to form a bud; the bud then lengthens to form an elongated sprout, which undergoes branching morphogenesis in a pattern dictated by the mesoderm. The gland lining is generated by formation of the lumen, and bipotent mammary stem cells give rise to luminal epithelial and myoepithelial cells. Key Concepts Mammary glands develop along ‘mammary lines’ that run from axilla (anterior) to groin (posterior) along both right and left sides of the ventral aspect of the mammalian trunk. Ectoderm cells of the mammary line migrate and aggregate to form individual discrete mammary placodes. The precise location of the mammary line and the placodes in the ectoderm is controlled by signals from underlying mesodermal tissues. Signals that control the formation of the mammary line and placodes include members of the WNT, FGF, NEUREGULIN and BMP signalling pathways. The Hedgehog signalling pathway is also involved. The TBX3 transcription factor is essential for the formation of the mammary placodes in mouse embryos, and mutations in the TBX3 gene have been found in patients with Ulnar‐mammary syndrome. The epithelial cells of the mammary bud produce parathyroid hormone‐related protein, which induces nearby mesoderm to form the mammary mesenchyme. Interactions between the mammary epithelial cells and the mammary mesenchyme are essential for further development and the subsequent elongation of the mammary bud to form a mammary sprout, which then undergoes branching morphogenesis in a pattern dictated by the deeper mesenchyme. Formation of the lumen of the embryonic gland involves fusion of microlumina created by local development of nonadhesive surfaces on the mammary epithelial cells and generates the epithelial lining which consists of an inner layer of luminal cells and an outer layer of myoepithelial cells. The cells of the mammary placode are determined to give rise to mammary epithelial cells; in the mammary bud, mammary stem cells can be detected that can give rise to both luminal and myoepithelial cells. Parallels, such as invasiveness, exist between the development of embryonic mammary glands and breast tumours and many of same molecules are involved.