Séminaire CIRI: Véronique MARTHIENS
Date / Heure
Date(s) - 21/09/2017
10 h 30 min - 11 h 30 min
salle des Thèses Chantal Rabourdin-Combes
Véronique MARTHIENS (Institut Curie/CNRS UMR144): « From centrosome dysfunctions to microcephaly: Mechanistic insights into brain susceptibility »
Centrosomes are the main microtubule-organizing centers of animal cells. They contribute to bipolar spindle positioning and assembly for correct segregation of chromosomes during mitosis. Centrosome dysfunction is reported in a wide spectrum of human diseases with different features, like cancer and brain growth disorders. The impact of centrosome abnormalities appears therefore to be tissue specific. We are interested in primary recessive microcephaly (MCPH), as mutations in several centrosome genes are directly responsible for this pathological condition where patients display brain size reduction and cognitive impairment without perturbation of body size. Microcephaly results from neural stem cell (NSC) loss at early stages of brain morphogenesis. Our lab is currently deciphering the particular susceptibility of embryonic NSCs to centrosome mutations using mouse as a model organism. With the aim of investigating this question, we have characterized centrosomes, mitotic spindle assembly and cell division in control brains from early to late stages of neurogenesis. We have identified unexpected tailoring of spindle assembly mechanisms during the course of normal brain development. We observed differences in spindle morphology that can be related to variations in the rate of mitotic errors in microcephaly brains with centrosome amplification. We propose that mitotic spindle features underlie NSC susceptibility when spindle assembly is challenged through centrosome mutations. These results raise new concepts regarding the etiology of MCPH.
Contact : Chloe Journo