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Fig. 4. Middle-ear skeletal phenotype of Hoxa2-/-;
Six2-/- and Hoxa2-/-;Six2+/-
mutant mice. (A-E) Dissected middle-ear skeleton from wild-type
(A), Hoxa2-/- (B), Hoxa2-/-;
Six2-/- (C,D) and Hoxa2-/-;
Six2+/- (E) E18.5 embryos. (A) Malleus (m), incus (i), gonial
bone (g) and tympanic ring (t) are derived from first arch; stapes (s) is
second arch-derived. (B-E) In the absence of Hoxa2, the stapes
disappears and duplicated first arch elements form in the second arch
(asterisks). The gonial bone abnormally extends to connect the wild-type
tympanic ring with its duplicated counterpart. (C) Removal of Six2
rescues the ectopic growth of the gonial bone. The malleal duplication is also
reduced (compare double-ended arrows in B and C). (D) The extent of the rescue
of the ectopic growth of the gonial bone in Hoxa2-/-;
Six2-/- was variable, but the ectopic gonial bone, when
present, never extended to reach the duplicated tympanic ring (arrowhead), as
invariably observed in Hoxa2-/- embryos (arrowhead in B).
(E) Complete reversal to a wild-type gonial bone was observed also in
Hoxa2-/-; Six2+/- embryos.
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