Leading science, pioneering therapies
CRM Publications

The essential requirement for Runx1 in the development of the sternum.

TitleThe essential requirement for Runx1 in the development of the sternum.
Publication TypeJournal Article
Year of Publication2010
AuthorsLiakhovitskaia A, Lana-Elola E, Stamateris E, Rice DP, Hof RJ van 't, Medvinsky AL
JournalDev Biol
Date Published2010 Apr 15
KeywordsAnimals, Bone and Bones, Core Binding Factor Alpha 2 Subunit, Embryo, Mammalian, Embryonic Development, Gene Expression Regulation, Developmental, In Situ Hybridization, Mice, Mice, Knockout, Sternum

Runx1 is highly expressed in chondroprogenitor and osteoprogenitor cells and in vitro experiments suggest that Runx1 is important in the early stages of osteoblast and chondrocyte differentiation. However, because Runx1 knockout mice are early embryonic lethal due to failure of hematopoiesis, the role of Runx1 in skeletogenesis remains unclear. We studied the role of Runx1 in skeletal development using a Runx1 reversible knockout mouse model. By crossing with Tie2-Cre deletor mice, Runx1 expression was selectively rescued in the endothelial and hematopoietic systems but not in the skeleton. Although Runx1(Re/Re) embryos survived until birth and had a generally normal skeleton, the development of mineralization in the sternum and some skull elements was significantly disrupted. In contrast to wild-type embryos, the sternum of E17.5 Runx1(Re/Re) embryos showed high levels of Sox-9 and collagen type II expression and lack of development of hypertrophic chondrocytes. In situ hybridization analysis demonstrated that, in contrast to the vertebrae and long bones, the sternum of wild-type embryos expresses high levels of Runx1, but not Runx2, the master regulator of skeletogenesis. Thus, although Runx1 is not essential for major skeletal development, it does play an essential role in the development of the sternum and some skull elements.

Alternate JournalDev. Biol.
PubMed ID20152828
Grant ListG0500950 / / Medical Research Council / United Kingdom
/ / Arthritis Research UK / United Kingdom
/ / Medical Research Council / United Kingdom