Title: [0045] Mutations of Myoclonin1 (EFHC1) disrupt radial and tangential migrations during brain development
Abstract: Heterozygous mutations in Myoclonin1/EFHC1 co-segregate with juvenile myoclonic epilepsy (JME) phenotypes. In adolescent patients with JME, they produce subtle malformations of cortical and subcortical architecture whereas homozygous F229L mutation in infancy induces severe brain pathology and death. However, the underlying pathological mechanisms for these observations remain unknown. We first demonstrated that EFHC1 is a microtubule-associated protein (MAP) involved in cell division and radial migration during cerebral corticogenesis. Next, we showed that JME mutations, including F229L, act in a dominant-negative manner to impair mitotic spindle organization. We also found that overexpression of EFHC1 mutants forms disrupted radial and tangential migration by affecting morphology of radial glia and migrating neurons. These results show how Myoclonin1/EFHC1 mutations disrupt brain development and could potentially produce structural brain abnormalities on which epileptogenesis is established.
Publication Year: 2013
Publication Date: 2013-06-09
Language: en
Type: article
Indexed In: ['crossref']
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