Regulation of Embryonic and Postnatal Development by the CSF-1 Receptor

V. Chitu, E. Richard Stanley

Research output: Contribution to journalArticle

30 Scopus citations

Abstract

Macrophages are found in all tissues and regulate tissue morphogenesis during development through trophic and scavenger functions. The colony stimulating factor-1 (CSF-1) receptor (CSF-1R) is the major regulator of tissue macrophage development and maintenance. In combination with receptor activator of nuclear factor κB (RANK), the CSF-1R also regulates the differentiation of the bone-resorbing osteoclast and controls bone remodeling during embryonic and early postnatal development. CSF-1R-regulated macrophages play trophic and remodeling roles in development. Outside the mononuclear phagocytic system, the CSF-1R directly regulates neuronal survival and differentiation, the development of intestinal Paneth cells and of preimplantation embryos, as well as trophoblast innate immune function. Consistent with the pleiotropic roles of the receptor during development, CSF-1R deficiency in most mouse strains causes embryonic or perinatal death and the surviving mice exhibit multiple developmental and functional deficits. The CSF-1R is activated by two dimeric glycoprotein ligands, CSF-1, and interleukin-34 (IL-34). Homozygous . Csf1-null mutations phenocopy most of the deficits of . Csf1r-null mice. In contrast, . Il34-null mice have no gross phenotype, except for decreased numbers of Langerhans cells and microglia, indicating that CSF-1 plays the major developmental role. Homozygous inactivating mutations of the . Csf1r or its ligands have not been reported in man. However, heterozygous inactivating mutations in the . Csf1r lead to a dominantly inherited adult-onset progressive dementia, highlighting the importance of CSF-1R signaling in the brain.

Original languageEnglish (US)
JournalCurrent Topics in Developmental Biology
DOIs
StateAccepted/In press - 2016

Keywords

  • CSF-1
  • CSF-1R
  • IL-34
  • Langerhans cells
  • Macrophages
  • Microglia
  • Neural progenitor cells
  • Osteoclasts
  • Paneth cells
  • Trophoblast cells

ASJC Scopus subject areas

  • Developmental Biology
  • Cell Biology

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