B. Kanzler et al., HOXA-2 RESTRICTS THE CHONDROGENIC DOMAIN AND INHIBITS BONE-FORMATION DURING DEVELOPMENT OF THE BRANCHIAL AREA, Development, 125(14), 1998, pp. 2587-2597
In Hoxa-2(-/-) embryos, the normal skeletal elements of the second bra
nchial arch are replaced by a duplicated set of first arch elements, W
e show here that Hoxa-2 directs proper skeletal formation in the secon
d arch by preventing chondrogenesis and intramembranous ossification,
In normal embryos, Hoxa-2 is expressed throughout the second arch mese
nchyme, but is excluded from the chondrogenic condensations. In the ab
sence of Hoxa-2, chondrogenesis is activated ectopically within the ro
stral Hoxa-2 expression domain to form the mutant set of cartilages. I
n Hoxa-2(-/-) embryos the Sox9 expression domain is shifted into the n
ormal Hoxa-2 domain. Misexpression of Sox9 in this area produces a phe
notype resembling that of the Hoxa-2 mutants. These results indicate t
hat Hoxa-2 acts at early stages of the chondrogenic pathway, upstream
of Sox9 induction. We also show that Hoxa-2 inhibits dermal bone forma
tion when misexpressed in its precursors. Furthermore, molecular analy
ses 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 norma
l second arch development. The implications of these results on the pa
tterning of the branchial area are discussed.