The collagen receptor DDR2 regulates proliferation and its elimination leads to dwarfism.
The discoidin domain receptor 2 (DDR2) is a member of a subfamily of receptor tyrosine kinases whose ligands are fibrillar collagens, and is widely expressed in postnatal tissues. We have generated DDR2-deficient mice to establish the in vivo functions of this receptor, which have remained obscure. These mice exhibit dwarfism and shortening of long bones. This phenotype appears to be caused by reduced chondrocyte proliferation, rather than aberrant differentiation or function. In a skin wound healing model, DDR2-/- mice exhibit a reduced proliferative response compared with wild-type littermates. In vitro, fibroblasts derived from DDR2-/- mutants proliferate more slowly than wild-type fibroblasts, a defect that is rescued by introduction of wild-type but not kinase-dead DDR2 receptor. Together our results suggest that DDR2 acts as an extracellular matrix sensor to modulate cell proliferation.
Labrador
J P
JP
European Molecular Biology Laboratory, Meyerhofstrasse 1, 69117 Heidelberg, Germany. Labrador@Socrates.Berkeley.edu
Azcoitia
V
V
Tuckermann
J
J
Lin
C
C
Olaso
E
E
Mañes
S
S
Brückner
K
K
Goergen
J L
JL
Lemke
G
G
Yancopoulos
G
G
Angel
P
P
Martínez
C
C
Klein
R
R
D000818:Animals; D017209:Apoptosis; D001846:Bone Development / Q000235:genetics / Q000502:physiology*; D002455:Cell Division; D019902:Chondrocytes / Q000378:metabolism / Q000502:physiology*; D003094:Collagen / Q000235:genetics / Q000378:metabolism; D000070818:Discoidin Domain Receptors; D004392:Dwarfism / Q000235:genetics* / Q000503:physiopathology; D005347:Fibroblasts / Q000378:metabolism / Q000502:physiology*; D006132:Growth Plate / Q000033:anatomy & histology; D006811:Humerus / Q000254:growth & development; D015151:Immunoblotting; D017403:In Situ Hybridization; D020287:In Situ Nick-End Labeling; D008682:Metatarsal Bones / Q000254:growth & development; D051379:Mice; D018345:Mice, Knockout; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics / Q000378:metabolism; D011975:Receptors, Mitogen / Q000235:genetics / Q000378:metabolism*; D012867:Skin / Q000166:cytology / Q000293:injuries / Q000378:metabolism; D013977:Tibia / Q000254:growth & development; D014945:Wound Healing
D011975:Receptors, Mitogen; D003094:Collagen; D000070818:Discoidin Domain Receptors; D020794:Receptor Protein-Tyrosine Kinases