Gas6 is dispensable for pubertal mammary gland development

PLoS One. 2018 Dec 11;13(12):e0208550. doi: 10.1371/journal.pone.0208550. eCollection 2018.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Axl Receptor Tyrosine Kinase
  • Epithelial Cells / metabolism
  • Female
  • Intercellular Signaling Peptides and Proteins / deficiency
  • Intercellular Signaling Peptides and Proteins / genetics
  • Intercellular Signaling Peptides and Proteins / metabolism*
  • Keratins / metabolism
  • Mammary Glands, Animal / growth & development
  • Mammary Glands, Animal / metabolism*
  • Mammary Glands, Animal / pathology
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Morphogenesis
  • Proto-Oncogene Proteins / genetics
  • Proto-Oncogene Proteins / metabolism
  • Puberty
  • Receptor Protein-Tyrosine Kinases / genetics
  • Receptor Protein-Tyrosine Kinases / metabolism
  • c-Mer Tyrosine Kinase / genetics
  • c-Mer Tyrosine Kinase / metabolism

Substances

  • Intercellular Signaling Peptides and Proteins
  • Proto-Oncogene Proteins
  • growth arrest-specific protein 6
  • Keratins
  • Mertk protein, mouse
  • Receptor Protein-Tyrosine Kinases
  • Tyro3 protein, mouse
  • c-Mer Tyrosine Kinase
  • Axl Receptor Tyrosine Kinase
  • AXL receptor tyrosine kinase, mouse