Atypical chemokine receptor ACKR2 controls branching morphogenesis in the developing mammary gland

Development. 2017 Jan 1;144(1):74-82. doi: 10.1242/dev.139733. Epub 2016 Nov 25.


Macrophages are important regulators of branching morphogenesis during development and postnatally in the mammary gland. Regulation of macrophage dynamics during these processes can therefore have a profound impact on development. We demonstrate here that the developing mammary gland expresses high levels of inflammatory CC-chemokines, which are essential in vivo regulators of macrophage migration. We further demonstrate that the atypical chemokine receptor ACKR2, which scavenges inflammatory CC-chemokines, is differentially expressed during mammary gland development. We have previously shown that ACKR2 regulates macrophage dynamics during lymphatic vessel development. Here, we extend these observations to reveal a novel role for ACKR2 in regulating the postnatal development of the mammary gland. Specifically, we show that Ackr2-/- mice display precocious mammary gland development. This is associated with increased macrophage recruitment to the developing gland and increased density of the ductal epithelial network. These data demonstrate that ACKR2 is an important regulator of branching morphogenesis in diverse biological contexts and provide the first evidence of a role for chemokines and their receptors in postnatal development processes.

Keywords: ACKR2; Branching; Chemokines; Mammary gland; Mouse.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Movement / genetics
  • Embryo, Mammalian
  • Female
  • Lymphangiogenesis / genetics
  • Lymphatic Vessels / embryology
  • Lymphatic Vessels / physiology
  • Macrophages / physiology
  • Mammary Glands, Animal / embryology*
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Morphogenesis / genetics*
  • Receptors, CCR / physiology*
  • Receptors, Chemokine / physiology*
  • Stromal Cells / metabolism


  • CC chemokine receptor 9
  • Receptors, CCR
  • Receptors, Chemokine