title: The genetics of auricular development and malformation: new findings in model systems driving future directions for microtia research.
abstract: Microtia is a term used to describe a wide array of phenotypic presentations of the outer ear. Although the majority of the cases are isolated in nature, much of our understanding of the causes of microtia has been driven by the identification of genes underlying syndromic forms where the anomaly co-presents with various other craniofacial and extra-craniofacial structural defects. In this review we discuss recent findings in mice deficient in Hoxa2, a key regulator of branchial arch patterning, which has necessitated a revision to the canonical model of pinna morphogenesis. The revised model will likely impact current classification schemes for microtia and, as we argue in this review, the interpretation of the developmental basis for various auricular malformations. In addition, we highlight recent studies in other mammalian species that are providing the first clues as to possible causes of at least some isolated anomalies and thus should now accelerate the search for the more elusive genetic contributions to the many isolated and non-syndromic cases of microtia. These findings, together with the application of new genome-level sequencing technologies and more thorough quantitative assessment of available mutant mouse resources, promise an exciting future for genetic studies in microtia.
authors.affiliation: Center for Developmental Biology & Regenerative Medicine, Seattle Children's Research Institute, Seattle, WA, USA; Department of Pediatrics (Craniofacial Medicine), University of Washington, Seattle, WA, USA; Department of Oral Health Sciences, University of Washington, Seattle, WA, USA; Department of Anatomy & Developmental Biology, Monash University, Clayton, Victoria, Australia. Electronic address: tccox@uw.edu.
authors.forename: Timothy C
authors.initials: TC
authors.lastname: Cox
authors.affiliation: Center for Developmental Biology & Regenerative Medicine, Seattle Children's Research Institute, Seattle, WA, USA; Department of Oral Health Sciences, University of Washington, Seattle, WA, USA.
authors.forename: Esra D
authors.initials: ED
authors.lastname: Camci
authors.affiliation: Center for Developmental Biology & Regenerative Medicine, Seattle Children's Research Institute, Seattle, WA, USA; Department of Oral Health Sciences, University of Washington, Seattle, WA, USA.
authors.forename: Siddharth
authors.initials: S
authors.lastname: Vora
authors.affiliation: Center for Developmental Biology & Regenerative Medicine, Seattle Children's Research Institute, Seattle, WA, USA; Department of Pediatrics (Craniofacial Medicine), University of Washington, Seattle, WA, USA.
authors.forename: Daniela V
authors.initials: DV
authors.lastname: Luquetti
authors.affiliation: Center for Integrative Brain Research, Seattle Children's Research Institute, Seattle, WA, USA; Department of Psychiatry and Behavioral Sciences, University of Washington, Seattle, WA, USA.
authors.forename: Eric E
authors.initials: EE
authors.lastname: Turner
mesh_terms: D000818:Animals; D065817:Congenital Microtia / Q000235:genetics*; D054644:Ear Auricle / Q000002:abnormalities* / Q000196:embryology; D006801:Humans
keywords: Anotia; Auricular development; Craniofacial microsomia; Goldenhar syndrome; Microtia; Mouse models; OAVS