The molecules that control the tissue-specific migration of fetal macrophages remain unknown. In Nature, Rantakari et al. show that PLVAP, a protein that forms diaphragms in fenestrated endothelial structures, selectively controls the seeding of fetal liver monocyte-derived macrophages to tissues in mice. Yolk-sack-derived and bone-marrow-derived macrophages are present at normal frequencies in adult PLVAP-deficient mice, which corresponds to the normal emergence of primitive progenitors in the yolk sack and AGM region of the embryonic mesoderm. PLVAP is expressed selectively on fetal liver sinusoidal endothelial cells starting at embryonic day 12.5. PLVAP-deficient mice, which completely lack diaphragms in the liver fenestrae during embryogenesis, have normal entry and differentiation of macrophage precursors in the fetal liver, while the exit of mature fetal liver monocytes is impaired. Fenestral diaphragms might assist the emigration of fetal liver monocytes by immobilizing chemotactic molecules or providing a substrate for adhesion.

Nature 538, 392–396 (2016)