Hoxa-2 restricts the chondrogenic domain and inhibits bone formation during development of the branchial area.
In Hoxa-2(-/- )embryos, the normal skeletal elements of the second branchial arch are replaced by a duplicated set of first arch elements. We show here that Hoxa-2 directs proper skeletal formation in the second arch by preventing chondrogenesis and intramembranous ossification. In normal embryos, Hoxa-2 is expressed throughout the second arch mesenchyme, but is excluded from the chondrogenic condensations. In the absence of Hoxa-2, chondrogenesis is activated ectopically within the rostral Hoxa-2 expression domain to form the mutant set of cartilages. In Hoxa-2(-/- )embryos the Sox9 expression domain is shifted into the normal Hoxa-2 domain. Misexpression of Sox9 in this area produces a phenotype resembling that of the Hoxa-2 mutants. These results indicate that Hoxa-2 acts at early stages of the chondrogenic pathway, upstream of Sox9 induction. We also show that Hoxa-2 inhibits dermal bone formation when misexpressed in its precursors. Furthermore, molecular analyses indicate that Cbfa1 is upregulated in the second branchial arches of Hoxa-2 mutant embryos suggesting that prevention of Cbfa1 induction might mediate Hoxa-2 inhibition of dermal bone formation during normal second arch development. The implications of these results on the patterning of the branchial area are discussed.
Kanzler
B
B
Max-Planck Institute of Immunobiology, Stübeweg 51, Germany.
Kuschert
S J
SJ
Liu
Y H
YH
Mallo
M
M
D000818:Animals; D001846:Bone Development / Q000502:physiology*; D001934:Branchial Region / Q000196:embryology / Q000254:growth & development*; D002356:Cartilage / Q000196:embryology / Q000254:growth & development; D050659:Core Binding Factor Alpha 1 Subunit; D015342:DNA Probes; D004622:Embryo, Mammalian / Q000166:cytology; D005314:Embryonic and Fetal Development; D018507:Gene Expression Regulation, Developmental / Q000235:genetics*; D005801:Genes, Homeobox / Q000235:genetics; D006257:Head / Q000196:embryology / Q000254:growth & development*; D006609:High Mobility Group Proteins / Q000235:genetics; D018398:Homeodomain Proteins / Q000235:genetics*; D006801:Humans; D017403:In Situ Hybridization; D051379:Mice; D018345:Mice, Knockout; D009363:Neoplasm Proteins; D055758:SOX9 Transcription Factor; D014157:Transcription Factors / Q000235:genetics
D050659:Core Binding Factor Alpha 1 Subunit; D015342:DNA Probes; D006609:High Mobility Group Proteins; D018398:Homeodomain Proteins; D009363:Neoplasm Proteins; D055758:SOX9 Transcription Factor; C527932:SOX9 protein, human; C527933:Sox9 protein, mouse; D014157:Transcription Factors