Embryonic Mammary Gland Development


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.

Keywords: ectoderm; mammary gland; mouse embryo; positional information; induction; epithelial–mesenchymal interactions; mammary stem cells; branching morphogenesis; invasiveness

Figure 1. (a) Diagrams showing the location of the ‘mammary line’ and mammary buds in E10.5 and E12.5 mouse embryos respectively. Pale blue indicates ectoderm, dark blue the mammary line and M the mammary bud (green). (b–f) Stages in embryonic development of the mouse mammary gland shown in transverse sections of the trunk. Scale bars represent 100 µm in each case. (b) ‘Mammary line’ (arrowed; base of ectoderm indicated by dotted line), E11.25 mouse embryo. (c) Mammary placode (base of ectoderm indicated by dotted line), E11.75 mouse embryo. (d) Early mammary bud, E12.5 mouse embryo. (e) Late mammary bud (mammary bulb), E14.5 mouse embryo. (f) Branching and lumen formation of an E17–18 mouse embryo, section shows the region that will form the primary duct.
Figure 2. Diagrams summarising the regulatory molecular networks involved in specifying the mammary line and in the formation of the mammary placodes. (a) Longitudinal section of trunk showing specification along the anteroposterior axis; (b) transverse section of trunk showing specification across the dorsoventral axis. (a) Section through anterior trunk and somites 14–16 only for clarity and specification of both mammary line (dark blue) and mammary placode 3 (MP3; green). Mesoderm coloured brown. Details of regulatory molecular interactions in the ventral tip of the somites, the mammary line and the mammary placode are shown in black boxes. RA, retinoic acid. Dotted orange arrows indicate mesenchymal signalling to ectoderm. Solid arrows indicate positive regulation which may be direct or indirect. (b) Section through MP3; colours and arrows as above. Ectoderm coloured pale blue. Black barred lines indicate negative regulation. Pink dots indicate dorsoventral BMP4 gradient.
Figure 3. Diagram summarising the regulatory molecular networks mediating epithelial–mesenchymal interactions in the mammary bud shown in transverse section. Colour coding as in Figure. Mammary mesenchyme coloured dark brown. Dotted arrows indicate signalling between mammary mesenchyme and mammary epithelium. Solid arrows indicate positive regulation. Pink dots indicate dorsoventral BMP4 gradient.
Figure 4. Diagrams summarising the regulatory molecular networks governing branching morphogenesis (a) and illustrating formation of the lumen (b) shown in transverse sections. Colour coding as in Figure. Deep mesenchyme (presumptive fat pad) coloured mauve.


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Further Reading

Brisken C and O'Malley B (2010) Hormone action in the mammary gland. Cold Spring Harbor Perspectives in Biology 2: a003178.

Inman JL, Robertson C, Mott JD, et al. (2015) Mammary gland development: cell fate specification, stem cells and the microenvironment. Development 142: 1028–1042.

Macias H and Hinck L (2012) Mammary gland development. Wiley Interdisciplinary Reviews: Developmental Biology 1: 533–557.

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Tickle, Cheryll, and Jung, Han‐Sung(Nov 2016) Embryonic Mammary Gland Development. In: eLS. John Wiley & Sons Ltd, Chichester. http://www.els.net [doi: 10.1002/9780470015902.a0026057]