Downregulation of Msx-2 expression results in chondrogenesis in the medial region of the avian mandible.

Homeobox-containing genes are thought to be regulators of pattern formation during vertebrate development. We have previously characterized regions in the developing chick mandible expressing either Msx-1 or Msx-2 in terms of their chondrogenic potential, rates of cell proliferation, and their correlation with regions of cell death. These experiments suggest that Msx-1 may be involved in outgrowth of the mandibular arch, and Msx-2 may be involved in delineating the non-chondrogenic region of the medial part of the mandibular arch. To further examine the possibility that expression of Msx-2 may be involved in preventing chondrogenesis in the medial region, mandibular arch explants from stage 23 chick embryos were cultured for 4 days in media in the absence of serum but in the presence of 20-30 microM Msx-2 sense or antisense oligonucleotides (18 mers). In explants grown in either control media or with the sense oligonucleotide two rods of cartilage separated by a cartilage free area located in the medial region of the mandible were formed. In explants treated with Msx-2 antisense oligonucleotide cartilage formation was observed in the medial region of the mandible resulting in the fusion of the two bilateral rods at the midline. These results suggest a negative relationship between Msx-2 expression and chondrogenesis in the medial region of the developing mandible.