Lumen formation in the developing mouse mammary gland

Abstract

The mammary gland is a system of hollow interconnecting tubes which develops from an invasive branching cord of epithelial cells. This ultrastructural study of the developing mammary gland focuses on how the lumen forms and establishes the polarized epithelial lining of the gland. The earliest signs of lumen formation are many small cavities and crevices lined with microvilli which appear at scattered sites throughout the branching cords and neck of the gland. It is suggested that these initial small lumina form quite simply by separation of cells whose opposing faces are non-adhesive. The continuous central lumen of the gland develops by fusion and enlargement of the many small lumina. The cells adjacent to the developing lumen will form the polarized epithelial lining of the gland. Excess, more basal, epithelial cells degenerate. The lumen begins to appear when the branching pattern is almost complete. Thus, during morphogenesis, invasion by the mammary gland epithelium involves penetration of the mesenchyme by a solid cord of cells. We suggest that this cellular organization may be a fundamental characteristic of invasive epithelia and that a crucial step in the development of malignant epithelial tumours is a change in cell organization from a polarizedcell sheet to a solid cord of cells which can invade.

Spatially coordinated cell cycle activity and motility govern mammary ductal growth and tip bifurcation

“…In mice, branching morphogenesis begins when a sprout rooted to the embryonic surface ectoderm is induced to branch around E16 and yields a rudimentary tree of 10-20 branches by birth (E19-20) (Macias & Hinck 2012, Lindström et al 2022). Lumen formation commences shortly before birth, and soon after, the final, bilayered structure of mammary ducts is established (Hogg et al, 1983). The inner layer of cells enclosing the lumen and outer layer of cells separated from the mesenchyme by a basement membrane, begin to segregate into distinct luminal and basal lineages already during late embryogenesis (Lilja et al 2018).…”

Spatially coordinated cell cycle activity and motility govern bifurcation of mammary branches

“…1 C ). The presence of microluminae that begin to emerge at ∼E17.5 ( Hogg et al, 1983 ) was confirmed in the elongating tips of both 5-d cultured explants and E18.5 mammary glands ( Fig. S2, C and D ).…”

“…In mice, branching morphogenesis begins when a sprout rooted to the embryonic surface ectoderm is induced to branch around embryonic day 16 (E16) and yields a rudimentary tree of 10–20 branches by birth (E19-20; Macias and Hinck, 2012 ; Spina and Cowin, 2021 ; Lindström et al, 2022 Preprint ). Lumen formation commences shortly before birth, and soon after, the final, bi-layered structure of mammary ducts is established, and ductal tree continues to grow isometrically to the body size ( Hogg et al, 1983 ). The inner layer of cells enclosing the lumen and outer layer of cells separated from the mesenchyme by a basement membrane, begin to segregate into distinct luminal and basal lineages during late embryogenesis ( Lilja et al, 2018 ).…”

Stabilization of epithelial β-catenin compromises mammary cell fate acquisition and branching morphogenesis

“…In hair follicles, the epithelium grows deeper into the dermis while encapsulating the dermal condensate that matures to dermal papilla, whereas the mammary bud gradually begins to proliferate and sprouts at ~E15.5 into a secondary mammary mesenchyme, the precursor of the adult fatty stroma, followed by onset of branching morphogenesis a day later . Mammary rudiments begin to branch as a solid cord of cells, and the bilayered ductal epithelium consisting of inner luminal and outer basal cells characteristic of the adult mammary gland becomes evident only after birth (Hogg et al, 1983;Myllymäki et al, 2023).…”