Abstract
In this study I aim to evaluate how the actin binding protein filamin B influences the development of cartilaginous structures of the skeleton, that when mutated, causes a range of disorders impacting large joints, limb development and craniofacial aspects of the body. Joints are an essential part of any organism as they allow for movement and are therefore extremely complex mechanical structures. The soft tissue elements of the joints are important because they provide these joints the ability to withstand immense forces from movement. Little is known about how filamin B is involved in the formation of the soft tissues in the developing joint and therefore the lack of understanding of how filamin B variants lead to the dislocation of the large joints seen in Larsen syndrome and other filamin B related syndromes. Joint development is critical in analysing how filamin B is involved in the formation and rare disease are an extremely valuable tool in approaching this. Rare genetic diseases such as Atelosteogenesis types I (AOI), Atelosteogenesis type III (AOIII), Boomerang dysplasia (BD) Spondylocarpotarsal synostosis syndrome (SCTS) and Larsen syndrome (LS) can all show different aspects of development that has been disrupted from various mutations within the filamin B gene. These are able to provide indications on what section of the filamin B protein, then when perturbed, leads to developmental abnormalities. In this study I used two mouse models tagged with the fluorophore mCherry and eGFP to track the development of joints in mice, in relation to filamin B both with and without the protein’s hinge-1.
My research found that both forms of hinge-1 included filamin B and hinge-1 excluded filamin B are found during development. It was also shown that red puncta indicating hinge-1 excluded filamin B is present within the joint capsule between the forming femur and tibia at E15.5. These red puncta were observed in the cells adjacent to the cellular membrane. During development the red puncta were exclusively defined to the joint spaces within all developing legs examined at E15.5. It was also shown that the critical point for knee joint ligament formation is between mouse embryonic time points E15.5 and E16.5.