Compatibility of ligands and receptors may influence the formation of interspecies chimeras. Ligand–receptor pairs found within a developing embryo participate in signaling pathways involved in embryogenesis. These ligand–receptor pairs cue subsequent steps of development to occur in an embryo. The same logic can apply to successful chimeric embryo development. (A) Injected donor stem cells (yellow cells) and host cells (blue, purple, and pink cells) may have similar or different ligand–receptor pairs that can influence the success of chimeras formed through blastocyst complementation. Chimera competency will likely increase when the ligand (brown circle) and receptor (blue shape attached to the purple cell) from two different species are compatible with one another. In contrast, incompatibility will likely prevent the formation of interspecies chimeras. (B) In addition, the cell–cell interactions between different species and tissues are currently being explored to better understand the compatibility of ligands and receptors, which are involved in the formation of interspecies chimera. The Venn diagram depicts human, rodent, and pig cell–cell relationships. The question marks allude to the unknown ligand–receptor pairs that may be crucial for development in chimeric animals. The species may have similarities or differences in these ligand–receptor pairs that may provide insight into interspecies chimera formation.