1 Introduction Colony-stimulating factor-1(CSF1) is a important hematopoietic growth factor that is involved in the proliferation,differentiation,and survival of monocytes,macrophages,and bone marrow progenitor cells[1].Its receptor(c-Fms) is known as the c-Fms proto-oncoprotein[2].By far the most definitive studies demonstrating biologic functions for CSF-1 in vivo are those in the op/op mutant mouse.The deficiency results from a single base-pair insertion in the coding region of the gene to product defective CSF-1.Mice homozygous for this mutation have significant osteopetrosis,low growth rate,low body weight as well as a toothless phenotype because of a severe deficiency of osteoclasts and mononuclear phagocytes,and are devoid of serum and tissue CSF-1 activity[7].In addition,they have defects in both male and female fertility,neural development,the dermis,and synovial membranes[8].Interestingly,c-Fms knock-out mice display a more severe osteopetrosis,reduced survival,and fewer tissue macrophages[9].This phenomenon strongly suggests the existence of another ligand for c-Fms.In 2008,Lin et alscreened a comprehensive set of recombinant secreted proteins and the extracellular domains transmembrane proteins using a high-throughput method.They noticed a previously undescribed ligand,designated Interleukin-34(IL34),which has a highly selective function in promoting monocyte viability.They then screened their library of extracellular domains of transmembrane proteins to block the activity of IL34 on monocytes and identified c-Fms as the possible receptor of IL34. 1 Introduction Colony-stimulating factor-1 (CSF1) is a important hematopoietic growth factor that is involved in the proliferation, differentiation, and survival of monocytes, macrophages, and bone marrow progenitor cells [1] .Its receptor (c- Fms) is known as the c-Fms proto-oncoprotein [2] .By far the most definitive studies demonstrating biologic functions for CSF-1 in vivo are those in the op / op mutant mouse.The deficiency results from a single base-pair insertion in the coding region of the gene to product defective CSF-1.Mice homozygous for this mutation have significant osteopetrosis, low growth rate, low body weight as well as a toothless phenotype because of a severe deficiency of osteoclasts and mononuclear phagocytes, and are devoid of serum In addition, they have defects in both male and female fertility, neural development, the dermis, and synovial membranes [8] .Interestingly, c-Fms knock-out mice display a more severe osteopetrosis reduced survival, and fewer tiss ue macrophages [9] .This phenomenon strongly suggests the existence of another ligand for c-Fms.In 2008, Lin et al. screened a comprehensive set of recombinant secreted proteins and the extracellular domains transmembrane proteins using a high-throughput method. undesired ligand, designated Interleukin-34 (IL34), which has a highly selective function in promoting monocyte viability. They then screened their library of extracellular domains of transmembrane proteins to block the activity of IL34 on monocytes and identified c-Fms as the possible receptor of IL34.