Msx1 and Dlx5 act independently in development of craniofacial skeleton, but converge on the regulation of Bmp signaling in palate formation

Mech Dev. 2006 Jan;123(1):3-16. doi: 10.1016/j.mod.2005.10.007. Epub 2005 Dec 5.


Msx and Dlx homeoproteins control the morphogenesis and organization of craniofacial skeletal structures, specifically those derived from the pharyngeal arches. In vitro Msx and Dlx proteins have opposing transcriptional properties and form heterodimeric complexes via their homeodomain with reciprocal functional repression. In this report we examine the skeletal phenotype of Msx1; Dlx5 double knock-out (DKO) mice in relationship with their expression territories during craniofacial development. Co-expression of Dlx5 and Msx1 is only observed in embryonic tissues in which these genes have independent functions, and thus direct protein interactions are unlikely to control morphogenesis of the cranium. The DKO craniofacial phenotypes indicate a complex interplay between these genes, acting independently (mandible and middle ear), synergistically (deposition of bone tissue) or converging on the same morphogenetic process (palate growth and closure). In the latter case, the absence of Dlx5 rescues in part the Msx1-dependent defects in palate growth and elevation. At the basis of this effect, our data implicate the Bmp (Bmp7, Bmp4)/Bmp antagonist (Follistatin) signal: in the Dlx5(-/-) palate changes in the expression level of Bmp7 and Follistatin counteract the reduced Bmp4 expression. These results highlight the importance of precise spatial and temporal regulation of the Bmp/Bmp antagonist system during palate closure.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Base Sequence
  • Bone Morphogenetic Protein 7
  • Bone Morphogenetic Proteins / antagonists & inhibitors
  • Bone Morphogenetic Proteins / genetics
  • Bone Morphogenetic Proteins / physiology*
  • Craniofacial Abnormalities / etiology
  • Craniofacial Abnormalities / genetics
  • DNA, Complementary / genetics
  • Ear, Middle / abnormalities
  • Ear, Middle / embryology
  • Facial Bones / embryology*
  • Gene Expression Regulation, Developmental
  • Homeodomain Proteins / genetics
  • Homeodomain Proteins / physiology*
  • MSX1 Transcription Factor / deficiency
  • MSX1 Transcription Factor / genetics
  • MSX1 Transcription Factor / physiology*
  • Mandible / abnormalities
  • Mandible / embryology
  • Mice
  • Mice, Knockout
  • Mice, Transgenic
  • Palate / abnormalities
  • Palate / embryology*
  • Phenotype
  • Signal Transduction
  • Skull / embryology*
  • Transforming Growth Factor beta / antagonists & inhibitors
  • Transforming Growth Factor beta / genetics
  • Transforming Growth Factor beta / physiology


  • Bone Morphogenetic Protein 7
  • Bone Morphogenetic Proteins
  • DNA, Complementary
  • Dlx5 protein, mouse
  • Homeodomain Proteins
  • MSX1 Transcription Factor
  • Msx1 protein, mouse
  • Transforming Growth Factor beta