Ror2, encoding a receptor-like tyrosine kinase, is required for cartilage and growth plate development.
Receptor tyrosine kinases often have critical roles in particular cell lineages by initiating signalling cascades in those lineages. Examples include the neural-specific TRK receptors, the VEGF and angiopoietin endothelial-specific receptors, and the muscle-specific MUSK receptor. Many lineage-restricted receptor tyrosine kinases were initially identified as 'orphans' homologous to known receptors, and only subsequently used to identify their unknown growth factors. Some receptor-tyrosine-kinase-like orphans still lack identified ligands as well as biological roles. Here we characterize one such orphan, encoded by Ror2 (ref. 12). We report that disruption of mouse Ror2 leads to profound skeletal abnormalities, with essentially all endochondrally derived bones foreshortened or misshapen, albeit to differing degrees. Further, we find that Ror2 is selectively expressed in the chondrocytes of all developing cartilage anlagen, where it essential during initial growth and patterning, as well as subsequently in the proliferating chondrocytes of mature growth plates, where it is required for normal expansion. Thus, Ror2 encodes a receptor-like tyrosine kinase that is selectively expressed in, and particularly important for, the chondrocyte lineage.
DeChiara
T M
TM
Regeneron Pharmaceuticals, Inc., Tarrytown, New York, USA.
Kimble
R B
RB
Poueymirou
W T
WT
Rojas
J
J
Masiakowski
P
P
Valenzuela
D M
DM
Yancopoulos
G D
GD
D000015:Abnormalities, Multiple / Q000196:embryology / Q000235:genetics*; D000595:Amino Acid Sequence; D000818:Animals; D001842:Bone and Bones / Q000002:abnormalities*; D002356:Cartilage / Q000002:abnormalities / Q000196:embryology*; D019070:Cell Lineage; D019902:Chondrocytes / Q000378:metabolism; D005314:Embryonic and Fetal Development / Q000235:genetics; D005326:Fetal Proteins / Q000172:deficiency / Q000235:genetics / Q000502:physiology; D018390:Gene Targeting; D017930:Genes, Reporter; D006132:Growth Plate / Q000196:embryology*; D017403:In Situ Hybridization; D051379:Mice; D018345:Mice, Knockout; D008969:Molecular Sequence Data; D009024:Morphogenesis / Q000235:genetics; D010641:Phenotype; D020794:Receptor Protein-Tyrosine Kinases / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D057050:Receptor Tyrosine Kinase-like Orphan Receptors; D011956:Receptors, Cell Surface / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D011993:Recombinant Fusion Proteins / Q000502:physiology; D015398:Signal Transduction
D005326:Fetal Proteins; D011956:Receptors, Cell Surface; D011993:Recombinant Fusion Proteins; C078717:ROR2 protein, human; D020794:Receptor Protein-Tyrosine Kinases; D057050:Receptor Tyrosine Kinase-like Orphan Receptors