PlexinD1 deficiency induces defects in axial skeletal morphogenesis.
Axial patterning in embryonic skeletogenesis associates with coordinated programming of somitogenesis and angiogenesis. As seen in endochondral bone formation, skeletogenesis is closely related to angiogenesis during development. PlexinD1 is a member of plexin family, is expressed in central nervous system and endothelium, and plays a role in blood vessel patterning and endothelium positioning during embryonic development. Here, we examined the effects of PlexinD1 deficiency on skeletogenesis. Three-dimensional micro CT examination revealed that PlexinD1 deficiency resulted in axial skeletal patterning defects including malformation in vertebral body and rib bone shape. Histological examination of the vertebral bodies and long bones showed that PlexinD1 deficiency altered the development of cartilage. PlexinD1 deficiency did not affect the levels of von Willebrand factor staining in relatively large vessels not attached but close to the vertebral body of mice. However, PlexinD1 deficiency reduced the von Willebrand factor (vWf) staining in most of the microvasculatures attached to the vertebral bone. PlexinD1 was expressed in osteoblastic cells and bone tissues of newborn and adult mice. As most of the homozygous knockout mice did not survive, we examined the role of PlexinD1 in bone formation in heterozygous adult mice subjected to bone marrow ablation. However, PlexinD1 heterozygous knockout did not reveal defects in new bone formation. In conclusion, PlexinD1 is involved in the patterning of axial skeletogenesis.
Kanda
Tomoatsu
T
Department of Molecular Pharmacology, Medical Research Institute, Tokyo Medical and Dental University, 3-10 Kanda-Surugadai 2-Chome, Chiyoda-ku, Tokyo 101-0062, Japan.
Yoshida
Yutaka
Y
Izu
Yayoi
Y
Nifuji
Akira
A
Ezura
Yoichi
Y
Nakashima
Kazuhisa
K
Noda
Masaki
M
D016475:3T3 Cells; D000818:Animals; D000831:Animals, Newborn; D019521:Body Patterning; D001854:Bone Marrow Cells / Q000378:metabolism; D001842:Bone and Bones / Q000002:abnormalities / Q000033:anatomy & histology / Q000196:embryology / Q000502:physiology; D047908:Intracellular Signaling Peptides and Proteins; D008562:Membrane Glycoproteins / Q000172:deficiency* / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008833:Microcirculation / Q000033:anatomy & histology; D009024:Morphogenesis; D009419:Nerve Tissue Proteins / Q000172:deficiency* / Q000235:genetics; D010006:Osteoblasts / Q000166:cytology / Q000502:physiology; D012863:Skeleton; D014057:Tomography, X-Ray Computed
D047908:Intracellular Signaling Peptides and Proteins; D008562:Membrane Glycoproteins; D009419:Nerve Tissue Proteins; C473552:Plxnd1 protein, mouse