HES1and HES5 are dispensable for cartilage and endochondral bone formation.pdf

Fax +41 61 306 12 34 E-Mail karger@karger.ch Original Paper Cells Tissues Organs 2010;192:17–27 DOI: 10.1159/000280416 HES1 and HES5 Are Dispensable for Cartilage and Endochondral Bone Formation C. Karlsson a C. Brantsing a R. Kageyama b A. Lindahl a a Institute for Laboratory Medicine, Department of Clinical Chemistry and Transfusion Medicine, Sahlgrenska University Hospital, Gothenburg , Sweden; b Institute for Virus Research, Kyoto University, Kyoto , Japan either by the HES1 and HES5 genes not being involved in cartilage and endochondral bone development or by func- tional redundancy between the genes belonging to the family of HES genes: that is, disruption of one gene could be compensated for by the activity of another. Our results fur- ther shed light on the compensatory reserves available dur- ing the developing cartilage and bone. Copyright ? 2010 S. Karger AG, Basel Introduction The molecular mechanisms regulating chondrogene- sis and endochondral bone formation are just beginning to be elucidated. These are highly complex processes and the progression of differentiation needs to be strictly reg- Key Words HES1  HES5  Cartilage development  Endochondral bone formation  Transgenic mice Abstract Notch signalling, via its downstream mediators HES1 and HES5, regulates development of several different tissues. In vitro studies suggest that these genes are also involved in chondrogenesis and endochondral bone formation. In order to investigate the importance of HES1 and HES5 for these developmental processes, mice lacking chondrogenic ex- pression of HES1 and HES5 were constructed by interbreed- ing HES5 –/– mice homozygous for the floxed HES1 allele (HES1 flox/flox ) with COL2A1-Cre transgenic mice, creating conditional HES1;HES5 double mutant mice. The formation of cartilage and endochondral bone was studied in these mice using histological and immunohistochemical stain- ings, including Alcian Bl