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Publication : Hoxa-2 restricts the chondrogenic domain and inhibits bone formation during development of the branchial area.

First Author  Kanzler B Year  1998
Journal  Development Volume  125
Issue  14 Pages  2587-97
PubMed ID  9636074 Mgi Jnum  J:49163
Mgi Id  MGI:1276793 Doi  10.1242/dev.125.14.2587
Citation  Kanzler B, et al. (1998) Hoxa-2 restricts the chondrogenic domain and inhibits bone formation during development of the branchial area. Development 125(14):2587-97
abstractText  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.
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