title: Cichlid fishes as a model to understand normal and clinical craniofacial variation.
abstract: We have made great strides towards understanding the etiology of craniofacial disorders, especially for 'simple' Mendelian traits. However, the facial skeleton is a complex trait, and the full spectrum of genetic, developmental, and environmental factors that contribute to its final geometry remain unresolved. Forward genetic screens are constrained with respect to complex traits due to the types of genes and alleles commonly identified, developmental pleiotropy, and limited information about the impact of environmental interactions. Here, we discuss how studies in an evolutionary model - African cichlid fishes - can complement traditional approaches to understand the genetic and developmental origins of complex shape. Cichlids exhibit an unparalleled range of natural craniofacial morphologies that model normal human variation, and in certain instances mimic human facial dysmorphologies. Moreover, the evolutionary history and genomic architecture of cichlids make them an ideal system to identify the genetic basis of these phenotypes via quantitative trait loci (QTL) mapping and population genomics. Given the molecular conservation of developmental genes and pathways, insights from cichlids are applicable to human facial variation and disease. We review recent work in this system, which has identified lbh as a novel regulator of neural crest cell migration, determined the Wnt and Hedgehog pathways mediate species-specific bone morphologies, and examined how plastic responses to diet modulate adult facial shapes. These studies have not only revealed new roles for existing pathways in craniofacial development, but have identified new genes and mechanisms involved in shaping the craniofacial skeleton. In all, we suggest that combining work in traditional laboratory and evolutionary models offers significant potential to provide a more complete and comprehensive picture of the myriad factors that are involved in the development of complex traits.
authors.affiliation: Department of Biology, University of Massachusetts Amherst, 221 Morrill Science Center South, 611 North Pleasant Street, Amherst, MA 01003, USA. Electronic address: kepowder@bio.umass.edu.
authors.forename: Kara E
authors.initials: KE
authors.lastname: Powder
authors.affiliation: Department of Biology, University of Massachusetts Amherst, 221 Morrill Science Center South, 611 North Pleasant Street, Amherst, MA 01003, USA. Electronic address: albertson@bio.umass.edu.
authors.forename: R Craig
authors.initials: RC
authors.lastname: Albertson
mesh_terms: D000818:Animals; D005075:Biological Evolution; D023681:Cichlids / Q000033:anatomy & histology / Q000196:embryology* / Q000235:genetics; D019465:Craniofacial Abnormalities / Q000196:embryology* / Q000235:genetics / Q000662:veterinary; D004195:Disease Models, Animal; D004625:Embryo, Nonmammalian / Q000473:pathology; D047108:Embryonic Development; D005247:Feeding Behavior; D005393:Fish Diseases / Q000196:embryology*; D018507:Gene Expression Regulation, Developmental; D059647:Gene-Environment Interaction; D058685:Genetic Pleiotropy; D006257:Head / Q000033:anatomy & histology* / Q000196:embryology; D006801:Humans; D008445:Maxillofacial Development / Q000235:genetics / Q000502:physiology*; D009432:Neural Crest / Q000196:embryology; D010641:Phenotype; D040641:Quantitative Trait Loci; D015398:Signal Transduction; D013045:Species Specificity; D015534:Trans-Activators / Q000235:genetics
chemical_list: D015534:Trans-Activators
keywords: Cichlids; Complex trait; Craniofacial; Evolutionary mutant; Morphological variation