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

Juhee Jeong, Xue Li, Robert J. McEvilly, Michael G. Rosenfeld, Thomas Lufkin, John L.R. Rubenstein

Research output: Contribution to journalArticlepeer-review

Abstract

Dlx transcription factors are implicated in patterning the mammalian jaw, base on their nested expression patterns in the first branchial arch (primordiurn for jaw) and mutant phenotypes; inactivation of Dlx1 and Dlx2 (Dlx1/2-l-) causes defects in the upper jaw, whereas Dlx5/6-l- 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-l- 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-l-, 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.

Original languageEnglish (US)
Pages (from-to)2905-2916
Number of pages12
JournalDevelopment
Volume135
Issue number17
DOIs
StatePublished - Sep 2008

Keywords

  • Branchial arch
  • Craniofacial
  • Dlx
  • Gbx2
  • Jaw
  • Mouse
  • Pou3f3

ASJC Scopus subject areas

  • Molecular Biology
  • Developmental Biology

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