Macrophage development: II. Early ontogeny of macrophage populations in brain, liver, and lungs of rat embryos as revealed by a lectin marker

Abstract

Earliest origins of macrophage populations in the central nervous system, the liver, and the lungs were studied in rat embryos aged between 10.5-11 days and 14 days of gestation, based on light and electron microscopic identification of macrophages using peroxidase-coupled isolectin B4 of Griffonia simplicifolia (GSA I-B4), which recognizes alpha-D-galactose groups on the cell membrane. During embryonic life macrophages and their precursors are GSA I-B4-positive and generally bereft of peroxidase-positive granules. At 10.5 days the yolk sac and embryonic circulations have just become joined, the brain has five vesicles but nerve cells are little differentiated, the liver exists as a diverticulum of the gut with fingerlike extensions of hepatocytes, and the lungs as a laryngotracheal groove. Macrophages and/or their precursors occurred in small numbers in embryonic mesenchyme and blood vessels but showed no special affinity for either liver or lung rudiments. The developing brain was the first organ to be colonized, beginning on prenatal day 12. The liver followed between days 12 and 13 and was succeeded by the lungs, beginning between days 13 and 14. Dividing macrophages were present in these organs at the outset of colonization and throughout the duration of the embryo series, indicating that from the beginning, replication of resident cells contributes to growth of the local population. Granulocyte precursors were first apparent in the liver around day 13; they are also GSA-positive but are distinguished from macrophages by their content of peroxidase-positive granules. Organ cultures of 13-day liver and lungs, and 14-day brain tissue, indicate that whereas isolated liver fragments support the formation of both granulocytes and macrophages, only the latter develop in brain or lung cultures. A resident population of macrophages evidently is set up very early in these organs, well before white cells colonize the spleen, bone marrow, and other future blood forming regions. The events outlined are seen as stages in an embryo-wide process that leads to establishment of macrophage populations in various organs.

Tissue macrophages act as cellular chaperones for vascular anastomosis downstream of VEGF-mediated endothelial tip cell induction

“…We reasoned that the embryonic hindbrain was ideally suited to study the role of the early, yolk sac-derived macrophages in angiogenesis, because avian studies had demonstrated that they colonise the brain by crossing the pial membranes and roof plate concomitantly with, but independently of, blood vessels. 30,31 Using the dual blood vessel/macrophage marker IB4 in combination with the macrophage-specific markers F4/80 and IBA1, 29,32,33 we confirmed that yolk sac-derived macrophages colonized the embryonic mouse brain independently of vessels, as reported for the chick (supplemental Figure 1, available on the Blood Web site; see the Supplemental Materials link at the top of the online article). We found that embryonic brain macrophages were always IB4-positive and that they expressed F4/80 by 11.5 dpc (Figure 1A-E; supplemental Figure 1).…”

Migration and differentiation of neural precursor cells can be directed by microglia

“…During embryonic development fetal macrophages͞microglia are detected in the CNS around E8 in mice and E12 in rat (33,34), a time-point well before the end of neurogenesis but before the onset of gliogenesis. The role of microglia cells during CNS development is generally believed to be to remove dead cells by phagocytosis.…”

Regulation of Microglial Development: A Novel Role for Thyroid Hormone

“…Isolectin B4 binds specifically to microglial and endothelial cells on sections of developing and adult rat CNS (Streit and Kreutzberg, 1987;Ashwell, 1991;Sorokin et al, 1992;Chamak et al, 1995). Microglial cells were stained with this lectin in the forebrain of both normal and hypothyroid newborn rats (P0).…”

“…2 B, P4 ). However, microglial cells were already present in the developing rat brain at E12 (Ashwell, 1991;Sorokin et al, 1992), 4 d before the beginning of MTU treatment (E16). Early transplacental transfer of thyroid hormones from the mother (Obregon et al, 1984;Porterfield and Hendrich, 1992) therefore might have influenced the early fetal development of the microglial cells.…”