Role of the Dlx Homeobox Genes in Proximodistal Patterning of the Branchial Arches: Mutations of Dlx-1, Dlx-2, and Dlx-1 and -2 Alter Morphogenesis of Proximal Skeletal and Soft Tissue Structures Derived from the First and Second Arches

• Published in: Developmental biology 1997-05, Vol.185 (2), p.165-184
• Main Authors: Qiu, Mengsheng, Bulfone, Alessandro, Ghattas, Ingrid, Meneses, Juanito J., Christensen, Lars, Sharpe, Paul T., Presley, Robert, Pedersen, Roger A., Rubenstein, John L.R.
• Format: Article
• Language: English
• Subjects: Animals; Branchial Region - embryology; Branchial Region - metabolism; Branchial Region - ultrastructure; Craniofacial Abnormalities - genetics; Craniofacial Abnormalities - pathology; Cytoskeletal Proteins; DNA Primers - chemistry; DNA-Binding Proteins - genetics; DNA-Binding Proteins - physiology; Gene Expression Regulation, Developmental - physiology; Homeodomain Proteins - genetics; Homeodomain Proteins - physiology; Mice; Mice, Mutant Strains; Morphogenesis - physiology; Mutagenesis, Site-Directed; RNA-Binding Proteins; Transcription Factors
• ISSN: 0012-1606; 1095-564X
• DOI: 10.1006/dbio.1997.8556

The Dlx homeobox gene family is expressed in a complex pattern within the embryonic craniofacial ectoderm and ectomesenchyme. A previous study established that Dlx-2 is essential for development of proximal regions of the murine first and second branchial arches. Here we describe the craniofacial phenotype of mice with mutations in Dlx-1 and Dlx-1 and -2. The skeletal and soft tissue analyses of mice with Dlx-1 and Dlx-1 and -2 mutations provide additional evidence that the Dlx genes regulate proximodistal patterning of the branchial arches. This analysis also elucidates distinct and overlapping roles for Dlx-1 and Dlx-2 in craniofacial development. Furthermore, mice lacking both Dlx-1 and -2 have unique abnormalities, including the absence of maxillary molars. Dlx-1 and -2 are expressed in the proximal and distal first and second arches, yet only the proximal regions are abnormal. The nested expression patterns of Dlx-1, -2, -3, -5, and -6 provide evidence for a model that predicts the region-specific requirements for each gene. Finally, the Dlx-2 and Dlx-1 and -2 mutants have ectopic skull components that resemble bones and cartilages found in phylogenetically more primitive vertebrates.