Molecular basis of variations in facial soft tissues: insights from cichlid fishes.

The human face serves as a crucial component of attractiveness and identity, playing a pivotal role in social interactions. Teleost fish models, particularly zebrafish, have offered valuable insights into the developmental and molecular mechanisms governing craniofacial skeletogenesis, owing to the molecular conservation in these processes. However, knowledge regarding the morphogenic processes shaping facial soft tissues remains surprisingly sparse. On the human side, most causal evidence comes from gene-phenotype associations in clinical genetics; however, these studies rarely provide cellular-resolution analyses of facial soft tissues, leaving tissue- and cell-type-specific mechanisms unresolved. The diverse family of Cichlidae constitute ∼10% of teleost fish species and represent an exceptional opportunity for evolutionary biology research due to their extensive ecological diversity and rapid speciation rates. Cichlid fishes also exhibit remarkable craniofacial morphological diversity, making them excellent models for studying both craniofacial skeletal and soft tissue morphogenesis. Utilizing the wealth of natural mutants within cichlid populations, this short review pitches cichlid fish models as valuable tools for investigating the genetic regulators and interactions underlying facial soft tissue formation. At present, most cichlid studies rely on comparative transcriptomics between closely related species with and without pronounced traits; these data are associative, and the regulatory hierarchy and primary drivers remain to be established through functional tests (e.g., genome editing). By synthesising developmental and regulatory mechanisms that influence morphological variations in facial soft tissues in cichlids and other model organisms, we create a blueprint for future molecular genetic investigations into facial diversity. Accordingly, we highlight the need for (i) causative functional studies in cichlids and (ii) cellular-resolution analyses of human facial soft tissues to bridge correlative and mechanistic evidence across systems.