Bmp4, short for Bone Morphogenetic Protein 4, is a significant protein in the bone morphogenetic protein family. It is involved in multiple biological processes such as embryonic morphogenesis, angiogenesis, and cell differentiation. Bmp4 functions through the BMP signaling pathway, which is crucial for early embryonic development, especially in the epiblast and extraembryonic lineages [2].

In corneal neovascularization (CNV), Bmp4 inhibits the formation of tip cells by reducing neutrophil extracellular traps (NETs) generation, disrupting the tip-stalk cell balance, and thus suppressing CNV [1].

In trophoblast development, Bmp4 signaling plays a role in the emergence and development of trophectoderm (TE) in mouse and human embryogenesis, and is also used in in vitro conversion of pluripotent stem cells into trophoblast [2,3].

In breast cancer, Bmp4 suppresses metastasis by inhibiting cholesterol biosynthesis [4].

In non-syndromic cleft lip with or without cleft palate (NSCL/P), Bmp4 enhances cell migration and promotes epithelial-mesenchymal transition (EMT) through the Smad1 signaling pathway, and abnormal Bmp4 may lead to NSCL/P [5].

In glioblastoma, Bmp4 inhibits invasion by promoting E-cadherin and claudin expression via the SMAD signaling pathway [6].

In human preimplantation embryos, Bmp4 supplementation triggers apoptosis [7].

In summary, Bmp4 is essential in various biological processes including embryonic development, angiogenesis, and cell-fate determination. Studies on Bmp4, especially through gene-knockout or conditional-knockout mouse models (not specifically detailed in provided refs but generally applicable in such research), contribute to understanding its role in diseases like CNV, breast cancer, NSCL/P, and glioblastoma, providing potential therapeutic targets for these conditions.