Altered SHH and FGF signaling causes polydactyly and syndactyly.
Shh domain was expanded along the
anterior–posterior and proximal–distal axis in
Sost–/– and
Sost–/–;
Sostdc1–/– relative to
WT and
Sostdc1–/– limb buds at E10.5
(A, arrows, bracket) and E1 1.5 (D). Downstream of Shh,
Gli1 expression was dramatically expanded in
Sost–/–;
Sostdc1–/– E11.5 limb buds
relative to all other genotypes (E, brackets). Grem1 expression
was absent in Shh positive region, and in
Sostdc1–/– and
Sost–/–;
Sostdc1–/– limbs the
Grem1 domain was reduced on the posterior side (B,
brackets). Fgf8 AER expression domain was expanded and
disorganized in Sost–/– and
Sost–/–;
Sostdc1–/– limbs, and on the
anterior side of the Sost–/–;
Sostdc1–/– limbs
Fgf8 expression was reduced in all time points examined (B
and F–G, arrows). A reduction in interdigital apoptosis was also
detected on the anterior side of
Sost–/–;
Sostdc1–/– limb buds at E12.5
(I, arrow).