Mechanisms in Midface Development and Dysmorphology

Abstract

Craniofacial asymmetry and dysmorphology in the sbse mutant mouse resembles the spectrum of anomalies associated with branchial arch disorders in human patients. Although relatively common, little is known about their etiology. Such disorders are characterized by mid- and lateral facial malformations, and are typically thought to be the result of a genetic or epigenetic events or insults during embryogenesis. In the mutant sbse variable midface asymmetry appears in concert with ectopic suture and synchondrosis fusion, postcranial defects, and ipsilateral ear phenotypes, within the first month after birth. In mutants, a rearrangement on Chromosome 4 disrupts the gene encoding Pleomorphic adenoma gene 1 (Plag1), a transcription factor associated with salivary gland tumor development. In this dissertation, I tested the role of Plag1 deficiency in the development of midface dysmorphology, and investigated the effect of the sbse mutation on embryonic gene expression.