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Fig. 2. Skeletal development. (A) At E13.5, mineralization of the clavicle (arrows) is delayed in the PAPPA^-/- compared with wild-type mice. (B) At E16.5, no caudal vertebrae were mineralized in the PAPPA^-/- mouse, whereas three to four caudal vertebral elements were undergoing mineralization in wild-type littermates (asterisk). The frontal (f) and interparietal (i) bones of the cranial vault are both undergoing mineralization at E16.5, but these processes are far less complete in PAPPA^-/- embryos. (C) Close-up of digits (arrow) and vertebrae (asterisk). Note an additional metatarsal had initiated mineralization in the wild-type compared with the PAPPA^-/- mice (arrow). (D) Close-up of cranial vault. The nasal (n), parietal (p) and occipital (o) bones are also delayed.

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