title: Developmental mechanisms underlying variation in craniofacial disease and evolution.
abstract: Craniofacial disease phenotypes exhibit significant variation in penetrance and severity. Although many genetic contributions to phenotypic variation have been identified, genotype-phenotype correlations remain imprecise. Recent work in evolutionary developmental biology has exposed intriguing developmental mechanisms that potentially explain incongruities in genotype-phenotype relationships. This review focuses on two observations from work in comparative and experimental animal model systems that highlight how development structures variation. First, multiple genetic inputs converge on relatively few developmental processes. Investigation of when and how variation in developmental processes occurs may therefore help predict potential genetic interactions and phenotypic outcomes. Second, genetic mutation is typically associated with an increase in phenotypic variance. Several models outlining developmental mechanisms underlying mutational increases in phenotypic variance are discussed using Satb2-mediated variation in jaw size as an example. These data highlight development as a critical mediator of genotype-phenotype correlations. Future research in evolutionary developmental biology focusing on tissue-level processes may help elucidate the "black box" between genotype and phenotype, potentially leading to novel treatment, earlier diagnoses, and better clinical consultations for individuals affected by craniofacial anomalies.
authors.affiliation: University of Massachusetts Lowell, Department of Biological Sciences, 198 Riverside Street, Olsen Hall, Room 619, Lowell, MA 01854, United States. Electronic address: jennifer_fish@uml.edu.
authors.forename: Jennifer L
authors.initials: JL
authors.lastname: Fish
mesh_terms: D000818:Animals; D005075:Biological Evolution; D019465:Craniofacial Abnormalities / Q000235:genetics*; D019143:Evolution, Molecular; D005145:Face / Q000196:embryology; D018507:Gene Expression Regulation, Developmental; D055785:Gene Knockdown Techniques; D056726:Genetic Association Studies; D014644:Genetic Variation; D006257:Head / Q000196:embryology; D006801:Humans; D036961:Matrix Attachment Region Binding Proteins / Q000235:genetics / Q000502:physiology; D008445:Maxillofacial Development / Q000235:genetics / Q000502:physiology*; D008648:Mesoderm / Q000166:cytology / Q000196:embryology; D009024:Morphogenesis; D009154:Mutation; D009432:Neural Crest / Q000166:cytology / Q000196:embryology; D012886:Skull / Q000196:embryology; D014157:Transcription Factors / Q000235:genetics / Q000502:physiology; D014714:Vertebrates / Q000196:embryology / Q000235:genetics
chemical_list: D036961:Matrix Attachment Region Binding Proteins; C521297:SATB2 protein, human; D014157:Transcription Factors
keywords: Cranial neural crest; Craniofacial anomalies; Evolution of development; Morphological variation; Satb2