The roles of different forms of cell death in the fate decision and morphogenesis of craniofacial organs

Regulated cell death (RCD) governs precise fate determination and morphogenesis during embryonic development through subtypes, including apoptosis, necroptosis, autophagy-dependent cell death, and ferroptosis. Of these, apoptosis, the most extensively studied RCD form, regulates cell elimination through both the intrinsic pathway, mediated by mitochondrial outer membrane permeabilization (MOMP), and the extrinsic pathway, activated by death receptors, thereby shaping craniofacial organ morphology. Notably, complex interactions exist between different death forms and their synergistic networks with key signaling pathways, such as BMP, FGF, and WNT, collectively regulating the balance between cell survival and death, which in turn influences the expression of genes critical for craniofacial structural development. This review systematically examines the various types of cell death involved in morphogenesis and fate determination during the development of craniofacial organs, highlighting their biological significance in organ morphogenesis and providing a theoretical foundation for developmental regeneration.