Translational medicine and neurogenetics
Regulation of cortical development in health and disease
Cortical lamination follows an inside-out sequence of neuronal placement and maturation that arises from the sequential birth and orderly migration of projection neurons and GABAergic interneurons. Cerebral cortical neurogenesis involves a tight coordination of multiple cellular activities including neuronal specification, migration and differentiation. Disrupting the completion of one or several of these steps often cause cortical malformations that lead to severe learning disabilities, mental retardation and epilepsy. Remarkably, mutations in proteins associated with the centrosome, the major microtubule organizer in animal cells, have been linked to several diseases of brain development. Those neurodevelopmental disorders are thought to involve abnormal neuronal proliferation, migration, differentiation and/or maturation, suggesting crucial roles of the centrosome at those different neuronal developmental stages. Interestingly growing evidences suggest a high sensitivity of the brain to centrosomal abnormalities.
What makes developing brain more affected by centrosomal defects? Does the centrosome have a specific protein signature during cortical development? What is the physiological importance of this signature? To which extent and how any alteration of this cortical signature contribute to neurodevelopmental pathologies?
Answers to those questions would be critical to interpret the pathological mechanisms that participate in the onset and the progression of neurological disorders. Despite the identification of hundreds of centrosomal proteins, the underlying mechanisms by which this organelle coordinates these different steps of cortical development remain largely unknown.
The major goal of the team is to better characterize the centrosome-regulated cellular and molecular pathways that contribute to the cortical embryonic neurogenesis in heath and disease.
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Nat Commun May 15, 2020 ; 11:2441 .
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Nature communications 13 May 2019 2019 ; : .
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Nat Commun May 13, 2019 ; 10:2129 .
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Cardiovasc Res Oct. 1, 2018 ; 114:1656-1666 .
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p27Kip1 Modulates Axonal Transport by Regulating alpha-Tubulin Acetyltransferase 1 Stability.
Cell Rep May 22, 2018 ; 23:2429-2442 .
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Hum Mol Genet Jan. 15, 2018 ; 27:224-238 .
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WD40-repeat 47, a microtubule-associated protein, is essential for brain development and autophagy.
Proc Natl Acad Sci U S A Oct. 12, 2017 ; 114:E9308-E9317 .
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Retinoic acid controls early neurogenesis in the developing mouse cerebral cortex.
Dev Biol Oct. 1, 2017 ; 430:129-141 .
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Sci Rep Sept. 19, 2016 ; 6:33377 .
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Nat Genet nov 2016 2016 ; 48:1349-1358 .
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