Lineage-specific assembly of primary cilia in the mouse embryo and stem cells
Dr Fiona Bangs, Developmental Biology Program, Memorial Sloan-Kettering Cancer Center, New York
DPAG Guest Speakers
Tuesday, 14 October 2014, 11am to 12pm
Sherrington Room, Sherrington Building, Department of Physiology, Anatomy and Genetics, South Parks Road
Primary cilia are required for cells to respond to signals essential for embryonic development and adult tissue homeostasis. Compromised cilia function leads to Ciliopathies characterised by polycystic kidneys, retinal degeneration, polydactyly and obesity. Loss of primary cilia in the adult can result in unregulated Hedgehog signaling leading to cancer. Many cells in vertebrates have a single primary cilium, but the tissue distribution of cilia has not been described systematically. To determine when and where primary cilia appear in the mouse embryo, we developed transgenic mice that express both the cilia marker ARL13B -mCherry and the centrosome marker Centrin2-GFP. As previously described, centrosomes (which template cilia) first appear at the 16-32 cell stage, however primary cilia are not present until after implantation at the time of cavitation where they are only found on cells of the epiblast. All subsequent epiblast derviatives are ciliated (ectoderm, mesoderm and definitive endoderm) in contrast, extraembryonic cells in the visceral endoderm and trophectoderm lineages have centrosomes but never assemble cilia. Extraembryonic endoderm stem (XEN) cells also lack cilia yet they express RFX3 and have mature basal bodies that are associated with transition zone proteins. NEDD9 and AURKA , members of the cilium disassembly pathway, are highly expressed in XEN cells. Inhibition of AURKA permits cilia assembly indicating that although XEN cells are ready and able to assemble cilia this only occurs when cilium disassembly is blocked. Lineage-dependent distribution of cilia is maintained throughout gestation, as such cells of extraembryonic origin in the placenta and yolk sac will not be able to respond to cilia dependent signals, like Hedgehog.