Proper intracellular organization is determinant for cell function and is achieved by the different cytoskeletons, actin, microtubules and intermediate filaments. In my group, we are investigating how the cell gets organized using the cytoskeleton. To do so, we are using the fibroblast and the muscle cell systems that present particular and complementary features.
Muscle cells have the particularity of containing hundreds of nuclei, resulting from the fusion of hundreds of myoblasts, that are evenly spaced just under the plasma membrane. To achieve this particular organization, nuclei have to undergo specific and successive types of nuclear movements.
The two first movements, centration and spreading, are microtubule-dependent but require different molecular motors and have therefore different characteristics. These movements are thought to rely on a major modification of the microtubule organization: since 1985 it is known that centrosomes, the microtubule organizing centers in the cell, disappear during muscle cell differentiation. The microtubule organization is transfered to the nucleus that recruits some centrosomal proteins and microtubule-nucleation factors. We recently found this is achieved by a particular isoform of Nesprin-1, an nuclear envelope-associated protein, expressed during muscle cell differentiation that recruit Akap-450, an anchor for microtubule-nucleators. The nuclear dispersion movement, on the other hand, relies on myofibrils contraction and nuclear envelope modifications.
We are now investigating the impact of nucleus-cytoskeleton interactions on nuclear shape and gene expression in healthy and pathological contexts, to propose new therapeutic strategies for muscle pathologies. We are developing muscle organoids to investigate contraction, cell architecture and reduce the use of animal models. Check “Bibliography” to know more.
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The Nucleus Science Talks
Since the first confinement, I am organizing the Nucleus Science Talks, a virtual seminar series with speakers from all over the world. With 60 speakers, more than 9 500 cumulated views (live + recorded), it is becoming a reference for researchers interested in the biology of the nucleus and the impact of its connection to the cytoskeleton.