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18697905
Dlx genes pattern mammalian jaw primordium by regulating both lower jaw-specific and upper jaw-specific genetic programs.

Development, 2008/9;135(17):2905-16.

Jeong J[1], Li X, McEvilly RJ, Rosenfeld MG, Lufkin T, Rubenstein JL

Affiliations

PMID: 18697905DOI: 10.1242/dev.019778

Impact factor: 6.862

Abstract
Dlx transcription factors are implicated in patterning the mammalian jaw, based on their nested expression patterns in the first branchial arch (primordium for jaw) and mutant phenotypes; inactivation of Dlx1 and Dlx2 (Dlx1/2-/-) causes defects in the upper jaw, whereas Dlx5/6(-/-) results in homeotic transformation of the lower jaw into upper jaw. Therefore, the 'Dlx codes' appear to regionalize the jaw primordium such that Dlx1/2 regulate upper jaw development, while Dlx5/6 confer the lower jaw fate. Towards identifying the genetic pathways downstream of Dlx5/6, we compared the gene expression profiles of the wild-type and Dlx5/6(-/-) mouse mandibular arch (prospective lower jaw). We identified 20 previously unrecognized Dlx5/6-downstream genes, of which 12 were downregulated and 8 upregulated in the mutant. We found a Dlx-regulated transcriptional enhancer in close proximity to Gbx2, one of the Dlx5/6-downstream genes, strongly suggesting that Gbx2 is a direct target of Dlx5/6. We also showed that Pou3f3 is normally expressed in the maxillary (prospective upper jaw) but not mandibular arch, is upregulated in the mandibular arch of Dlx5/6(-/-), and is essential for formation of some of the maxillary arch-derived skeleton. A comparative analysis of the morphological and molecular phenotypes of various Dlx single and double mutants revealed that Dlx1, 2, 5 and 6 act both partially redundantly and antagonistically to direct differential expression of downstream genes in each domain of the first branchial arch. We propose a new model for Dlx-mediated mammalian jaw patterning.
MeSH terms
Animals; Base Sequence; Body Patterning; Branchial Region; Enhancer Elements, Genetic; Forkhead Box Protein L2; Forkhead Transcription Factors; Gene Expression Profiling; Gene Expression Regulation, Developmental; Genome; Homeodomain Proteins; Jaw; Mice; Molecular Sequence Data; Mutation; Nerve Tissue Proteins; Organ Specificity; POU Domain Factors; Phenotype; RNA, Messenger; RNA, Untranslated; Repressor Proteins; Signal Transduction; Transcription Factors; Transcription, Genetic
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