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

Development. 2008 Sep;135(17):2905-16. doi: 10.1242/dev.019778.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Base Sequence
  • Body Patterning / genetics*
  • Branchial Region / cytology
  • Branchial Region / embryology
  • Enhancer Elements, Genetic / genetics
  • Forkhead Box Protein L2
  • Forkhead Transcription Factors / genetics
  • Forkhead Transcription Factors / metabolism
  • Gene Expression Profiling
  • Gene Expression Regulation, Developmental
  • Genome / genetics
  • Homeodomain Proteins / genetics*
  • Homeodomain Proteins / metabolism
  • Jaw / embryology*
  • Mice
  • Molecular Sequence Data
  • Mutation / genetics
  • Nerve Tissue Proteins / genetics
  • Nerve Tissue Proteins / metabolism
  • Organ Specificity / genetics
  • POU Domain Factors / genetics
  • POU Domain Factors / metabolism
  • Phenotype
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • RNA, Untranslated / genetics
  • Repressor Proteins / metabolism
  • Signal Transduction / genetics
  • Transcription Factors / genetics*
  • Transcription, Genetic


  • Distal-less homeobox proteins
  • Forkhead Box Protein L2
  • Forkhead Transcription Factors
  • Foxl2 protein, mouse
  • Gbx2 protein, mouse
  • Homeodomain Proteins
  • Nerve Tissue Proteins
  • POU Domain Factors
  • RNA, Messenger
  • RNA, Untranslated
  • Repressor Proteins
  • Transcription Factors
  • Pou3f3 protein, mouse