Project: Genetics of cortical gyral dysgenesis and pathophysiology of tubulin-related malformations of cortical development

Intellectual disability (ID) and epilepsy, originally of unknown cause, are now known to result from many defects including malformations of cortical development (MCD) and perturbation of neuronal communication and synaptic function. Over the past few years, the importance of cytoskeletal components in cortical development has emerged from a body of functional and genetic data, including the recent discoveries, by partners of this proposal and others, of patients with MCD such as lissencephaly/pachygyria and polymicrogyria carrying mutations in TUBA1A, TUBB2B TUBB3 and TUBA8. In addition to genetic and molecular approaches aiming to define a comprehensive spectrum of MCD, the objective of our proposal will be focused on the definition of TUBA1A, TUBB2B, TUBB3, and their corresponding MTs roles during cortical development, to understand how tubulins dysfunction lead to abnormal neuronal migration, differentiation and / or proliferation, and point out functional differences that may underlie cortical malformations. The consortium involves groups with recognized complementary skills and experience. They have already achieved successful collaborations and are aggregated according to their expertise in clinical assessment, imaging and molecular diagnosis of MCD (Partners 1 and 2); molecular pathology of MCD (Partner1 and 2), development of animal models of developmental brain disorders (Partner1 and 3). In addition to this complementary expertise and sound scientific added-value, the three Partners own the necessary state-of-the-art equipment and technical platforms.

Network E-Rare-2
Call 3rd Joint Call for Research Projects on Rare Diseases

Project partner

Number Name Role Country
1 INSERM Coordinator France
2 IRCCS Stella Maris Foundation Partner Italy
3 Research Institute of Molecular Pathology Partner Austria