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Fig. 1. Gli3 and Hoxd12 interact genetically during limb
development. E17.5-18.5 limb skeletons (left and middle two columns), and
E11.5-12.5 hindlimb bud Shh expression (right column) of (A) weak
Tg-Hoxd12 line (identical to wild type, +/+), (B)
Gli3+/-, (C)
Tg-Hoxd12;Gli3+/-, (D)
Gli3-/- and (E)
Tg-Hoxd12;Gli3-/- embryos. Hindlimb long bones
(fe, femur; ti, tibia; fi, fibula) and digits (I-V) are marked for
Tg-Hoxd12. Extra digits (*) with distinct identities are
marked for Gli3+/- and
Tg-Hoxd12;Gli3+/-. Anterior is top, posterior
bottom, for all panels except column 2 (anterior right, posterior left).
Gli3+/- (B) have only an extra digit I (arrow), whereas
Tg-Hoxd12;Gli3+/- (C) have more extensive
polydactyly with posterior transformations and very distinct digit identities.
By contrast, polydactyly in Tg-Hoxd12;Gli3-/- (E)
is unchanged from Gli3-/- (D); both have 7-9 forelimb and
5-7 hindlimb digits that are all short and predominantly digit I-like (see
also Fig. 2). Note that in some
cases the posterior-most Gli3-/- digits show variable
cartilage staining in an otherwise clear, amorphous region that is suggestive
of a rudimentary third (middle) phalanx formation (e.g. D,E). In other
instances (e.g. Fig. 2F), such
rudiments are completely absent from all digits. Unlike digit phenotypes, long
bone shortening worsens progressively, and is severest in
Tg-Hoxd12;Gli3-/-. Normal Shh expression
(E11.5-12, right column) in Tg-Hoxd12 (A) and
Gli3+/- (B) is lost by E12.5, whereas some
Tg-Hoxd12;Gli3+/- (C) have broad, deregulated
Shh at 
E12. By contrast,
Tg-Hoxd12;Gli3-/- (D) and
Gli3-/- (E) both show only focal ectopic Shh
(arrow) at E12.5.
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