Specification of tissue-resident macrophages during organogenesis

Science. 2016 Sep 9;353(6304):aaf4238. doi: 10.1126/science.aaf4238. Epub 2016 Aug 4.


Tissue-resident macrophages support embryonic development and tissue homeostasis and repair. The mechanisms that control their differentiation remain unclear. We report here that erythro-myeloid progenitors in mice generate premacrophages (pMacs) that simultaneously colonize the whole embryo from embryonic day 9.5 in a chemokine-receptor-dependent manner. The core macrophage program initiated in pMacs is rapidly diversified as expression of transcriptional regulators becomes tissue-specific in early macrophages. This process appears essential for macrophage specification and maintenance, as inactivation of Id3 impairs the development of liver macrophages and results in selective Kupffer cell deficiency in adults. We propose that macrophage differentiation is an integral part of organogenesis, as colonization of organ anlagen by pMacs is followed by their specification into tissue macrophages, hereby generating the macrophage diversity observed in postnatal tissues.

Publication types

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

MeSH terms

  • Animals
  • CX3C Chemokine Receptor 1
  • Cell Differentiation / genetics*
  • Embryo, Mammalian / cytology*
  • Embryonic Development
  • Embryonic Induction
  • Erythroid Precursor Cells / cytology
  • Erythroid Precursor Cells / metabolism
  • Female
  • Gene Expression Regulation, Developmental*
  • Hematopoiesis / genetics
  • Hematopoiesis / physiology
  • Inhibitor of Differentiation Proteins / metabolism
  • Kupffer Cells / cytology
  • Kupffer Cells / metabolism
  • Macrophages / cytology*
  • Macrophages / metabolism
  • Mice
  • Mice, Mutant Strains
  • Myeloid Progenitor Cells / cytology*
  • Myeloid Progenitor Cells / metabolism
  • Organ Specificity
  • Organogenesis*
  • Receptors, Chemokine / genetics
  • Transcriptome


  • CX3C Chemokine Receptor 1
  • Cx3cr1 protein, mouse
  • Inhibitor of Differentiation Proteins
  • Receptors, Chemokine
  • Idb3 protein, mouse