Biology of centrosomes and Cilia
Group leader : Renata Basto
The Basto lab is interested in studying the basic mechanisms that regulate centriole and cilia biogenesis and to understand how dysfunction of these organelles can lead to the establishment of developmental defects and disease. The centrosome is the major microtubule-organising center of animal cells. It contains two centrioles (microtubule-based cylindrical organelles) that recruit and organise a large number of proteins to form the pericentriolar material. In a normal cell, the two centrioles of the centrosome replicate only once during the cell cycle to ensure the formation of a bipolar spindle that accurately segregates the chromosomes into two daughter cells. Recently, we have shown that centrosome amplification, the presence of supernumerary centrosomes in stem cells can lead to tumour formation. We are therefore focusing on better defining the nature of the link between centrosomes and cancer. We use two different model organisms, the fruit fly Drosophila melanogaster and mouse as a vertebrate model system. Through a combination of complementary approaches, our target objectives are therefore to identify and dissect the molecular pathways that allow transformation of stem cells when extra centrosomes are present.
Figure 1 : A- The two centrosomes of the cell (shown in yellow) nucleate and organize the MT network (red) to assemble a bipolar mitotic spindle. The chromosomes are shown in blue. B- Electron microscopy (EM) picture of a cross section of Drosophila sperm tail flagellum.
In addition to their role at the centrosome, centrioles can also be found close to the plasma membrane where they behave as basal bodies. Basal bodies nucleate cilia or flagella, microtubule microtubule-based structures with crucial roles in motility, sensory perception and signaling. Recently, it has been recognized that the majority of the cells in the human body contain primary cilia and that mutations that affect basal body and /or cilia structure can lead to the establishment of severe developmental defects and pathologies such as cancer. We are also investigating the basic mechanisms that regulate basal body duplication and ciliogenesis and how defects in these structures can lead to tumourigenesis.
Figure 2: A. Extra centrosomes in the mouse neural stem cells cause multipolar divisions, which are normally unviable. B. Inhibition of neural stem cell death results in the progressive degeneration of the mammalian brain.