In the Absence of BMP2 and BMP4, Osteogenesis Begins During Early Embryonic Development

<div><p>(A–D) Sagittal sections of forelimb from E15.5 embryos. (A and B) Stained with toluidine blue. (A) Distal ulna from wild-type embryo, (B) distal ulna/radius from <i>Bmp2^C/C</i>; <i>Bmp4^C/C</i>; <i>Prx1::cre</i> embryo. Mineralized cartilage is shown by dark purple and osteoid is shown by light blue (red asterisk). (C and D) Humeri sections were hybridized with digoxigenin labeled riboprobe for <i>ColI</i>. (C) Section of wild-type humerus from E15.5 embryo, (D) from <i>Bmp2^C/C</i>; <i>Bmp4^C/C</i>; <i>Prx1::cre</i> E15.5 embryo.</p><p>(E–H) Sagittal sections of zeugopod from E17.5 embryos. (E and F) Stained with toluidine blue while G and H are stained for TRAP (brown stain, red arrow). (E and G) E17.5 proximal radius from wild-type embryo, (F and H) E17.5 proximal ulna/radius from <i>Bmp2^C/C</i>; <i>Bmp4^C/C</i>; <i>Prx1::cre</i> embryo. Although vascularization occurs in the absence of BMP2 and BMP4, few osteoclasts are observed in the mineralized cartilage in <i>Bmp2^C/C</i>; <i>Bmp4^C/C</i>; <i>Prx1::cre</i> mice. Please note all the panels other than (G) and (H) are photographed at ×20, while (G) and (H) were photographed at ×40.</p><p>(I and J) Sections of newborn proximal radius (I) from control animal and newborn proximal ulna/radius (J) from <i>Bmp2^C/C</i>; <i>Bmp4^C/C</i>; <i>Prx1::cre</i> animal were stained with toluidine blue. Red arrow shows the bone marrow cavity in (E) and (I). Note that bone collar (red *) forms at the right time and place in the absence of BMP2 and BMP4. Also note that since <i>Bmp2^C/C</i>; <i>Bmp4^C/C</i>; <i>Prx1::cre</i> mice occasionally have only one bone in zeugopod and the elbow joint is occasionally fused, it is difficult to distinguish between the ulna and the radius.</p>