Phase separation and condensates in craniofacial development

Biomolecular condensates formed by liquid-liquid phase separation (LLPS) have emerged as a major mode of intracellular organization, and their roles in craniofacial development are only beginning to be defined. In this review, we synthesize evidence that phase separation and condensate biology influences craniofacial morphogenesis at multiple levels, from transcriptional control in neural crest-derived lineages to signaling integration, mechanosensing, and the formation of mineralized tissues. Nuclear condensates formed by transcription factors and chromatin regulators are implicated in clefting and craniofacial syndromes are highlighted as modulators of local gene expression programs and cell fate decisions. Condensate-mediated regulation of mechanosensitive pathways and nucleolar function in osteogenic and chondrogenic cells is discussed in relation to craniofacial bone, cartilage, and sutural growth. In parallel, we examine extracellular phase-separation-like and LLPS-adjacent phenomena in enamel and dentin biomineralization, including self-assembly of enamel matrix proteins and polymer-induced liquid precursors that concentrate ions and guide apatite organization. Shared principles, conceptual distinctions, and outstanding questions are outlined, with emphasis on experimental strategies that link condensate or phase-behavior properties to craniofacial development, malformation and tissue repair.