Impaired skeletal development in Smad4 mutant mice.
A and B, immunostaining of Smad4 on the forelimb on the control and mutant mice at E12.5. Arrows indicate chondrocytes and arrowheads indicate perichondrial cells. A3 and B3 are overlay images for A1/2 and B1/2, respectively. A4 and B4 are high magnification images in the areas outlined in A3 and B3. C–J, whole mount view of Smad4 CKO mice at E14.5–18.5. Arrows indicate control forelimb (C, E, and G) and hindlimb (I), or mutant forelimb (D, F, and H) and hindlimb (J). K–R, skeletons of E15.5–18.5 embryos stained with Alizarin red (calcified tissue) and Alcian blue (cartilage). K, M, O, and Q are controls and L, N, P, and R are mutants. In K–P, arrows, arrowheads, and unnotched arrows indicate humerus, radius, and ulna, respectively. In Q and R, arrows, arrowheads, and unnotched arrows indicate femur, fibula, and tibia, respectively.