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Fig. 6. The defects in skeletogenesis in Ror2^{W749FLAG/W749FLAG} mutants stem from abnormalities in early chodrogenic condensation and specification of the distal digital joint. (A-I) Whole-mount cartilage staining of Ror2^{W749FLAG/W749FLAG} (center) and heterozygous litter-matched E14.5 embryos (left), compared with Ror2^{TMlacZ/TMlacZ} embryos (right). (A-C) Lateral view showing the reduction of all skeletal elements in Ror2^{W749FLAG/W749FLAG} and Ror2^{TMlacZ/TMlacZ} embryos. (D-F) Dorsal view of the thoracic spine. Ror2^{W749FLAG/W749FLAG} and Ror2^{TMlacZ/TMlacZ} vertebrae are hypoplastic and irregularly stacked (arrows). (G-I) Dissected forelimbs (top) and hindlimbs (bottom), showing reduced cartilage condensations in the homozygous mutant embryos. Note the absence of joint formation in the phalanx anlagens of the mutant forelimbs (arrowheads) and the greater reduction of condensation size in the Ror2^{TMlacZ/TMlacZ} limbs. (J-T) Cleared skeletal preparations from control Ror2^+/W749FLAG (left), littermate Ror2^{W749FLAG/W749FLAG} (center) and Ror2^{TMlacZ/TMlacZ} (right) E18.5 embryos. (J-L) Side view of skulls showing shortened nasal bones in the homozygous mutant embryos. (M-O) Dorsal view of ribcages showing smaller and tilted vertebrae in Ror2^{W749FLAG/W749FLAG} and Ror2^{TMlacZ/TMlacZ} embryos (N,O, arrows). Fused ribs were present with full penetrance in Ror2^{TMlacZ/TMlacZ} embryos (O). (P-R) View of the hindlimb showing delayed ossification of metacarpals and phalanges in the homozygous mutant embryos (Q,R, arrows) and a severely misshapen Ror2^{TMlacZ/TMlacZ} stylopod (arrowhead). (S-U) Comparison of control Ror2^+/W749FLAG and Ror2^{W749FLAG/W749FLAG} forepaws (S,T) with a Ror2^-/- forepaw (U). Note the normal number of phalanges in the Ror2^-/- digits despite being as affected in length as the Ror2^{W749FLAG/W749FLAG} digits.

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