The function of BBSome in regulation of cilia and Wnt signaling in bone marrow stromal cells.

Primary cilia are microtubule-based organelles projecting from the cell surface, where their principal function is to sense extracellular cues and mediate multiple developmental signalling cascades. Cilia dysfunction gives rise to a group of genetic disorders known as ciliopathies. They manifest with diverse symptoms across multiple organs and tissues. One such disorder is Bardet-Biedl syndrome (BBS), most commonly caused by mutations in proteins forming the BBSome complex that is responsible for trafficking signalling receptors into and out of the cilium. Among BBSome proteins, BBS4 is critical for complex formation and its loss results in the absence of a functional BBSome. This thesis focuses on BBSome complex and its tissue-specific functions in bone marrow mesenchymal stromal cells (BM MSCs). First, we established a control and Bbs4-deficient BM MSCs model cell line. Analysis of the cilia length revealed no alterations between the control and BBS conditions. Next, we investigated alterations in cilia-dependent signalling pathways caused by Bbs4 deficiency. We found that loss of the BBSome leads to dysregulations in both Hedgehog (HH) and WNT pathways. Last, we examined how BBSome loss alters stromal cell lineage fate decisions. We found that the BBSome in bone marrow regulates the signalling...