Abstract
Mammary gland development is a complex and dynamic process that occurs mainly postnatally. Ductal elongation and branching morphogenesis are regulated by a plethora of factors, including cytokines, hormones, growth factors and the extracellular matrix. Gas6 is a secreted gamma-carboxylated protein that binds to a family of receptors tyrosine kinase receptors known as the TAMR family (Tyro3, Axl, Mer). Gas6 function in developmental processes has been shown in nervous, reproductive and immune systems. In this study, we found that Gas6 is highly expressed in virgin adult mammary glands but declines during pregnancy and lactation. Specifically, Gas6 is highly expressed in luminal and basal mammary epithelial cells during puberty and adulthood, while TAMR expression is low. Mammary whole mount analysis revealed that Gas6 germline deletion does not impact ductal elongation, branching morphogenesis or terminal end bud formation. Masson’s trichrome staining showed that collagen deposition is similar in Gas6-/- mice as compared to wildtype mice. Gas6-/- mammary glands presented an organized luminal and myoepithelial bilayer of cells, and the proportion of mammary stem cells was unchanged in Gas6-/- mammary glands as compared to wildtype. Finally, proliferation of epithelial cells and macrophage number were similar in both groups. These studies suggest that Gas6 is not essential for pubertal mammary gland development in nulliparous mice.
Highlights
Mammary gland development is a carefully orchestrated process that occurs primarily postnatally
Growth arrest-specific 6 (Gas6) is highly expressed in basal and luminal cells during mammary gland development
Gas6 is highly expressed in virgin adult glands (10 and 12 weeks), its expression declines during pregnancy and lactation (S1 Fig)
Summary
Mammary gland development is a carefully orchestrated process that occurs primarily postnatally. This developmental program is characterized by ductal elongation and branching morphogenesis that results in a functional epithelial ductal tree. Several factors coordinate the invasion of epithelial cells through the mammary fat pad including local growth factors and cytokines, circulating hormones, extracellular matrix proteins and epithelial-stroma cell. Komen CCR16377665 (H.L.M) and National Cancer Institute (NIH) R01 CA212518 (H.L.M.). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript
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