Myoclonin1/EFHC1 in cell division, neuroblast migration, synapse/dendrite formation in juvenile myoclonic epilepsy

This chapter presents recent works on Myocloni1/ EFHC1 a protein encoded by an epilepsy causing gene of juvenile myoclonic epilepsy (JME), one of the most frequent forms of idiopathic or genetic generalized epilepsies.

Myoclonin 1/EFHC1 is a microtubule-associated protein involved in the regulation of cell division. In vitro, EFHC1 loss of function disrupted mitotic spindle organization, impaired M phase progression, induced microtubule bundling and increased apoptosis. EFHC1 impairment in the rat developing neocortex by ex vivo and in utero electroporation caused a marked disruption of radial migration. This effect was a result of cortical progenitors failing to exit the cell cycle. On the other hand, defects in the radial glia scaffold organization and in the locomotion of postmitotic neurons. Mutant analysis of Defhc1 loss- and gain-of-function alleles in vivo in Drosophila revealed a number of neuronal defects, including abnormal synaptic development characterized by extensive satellite bouton formation, increased frequency of spontaneous neurotransmitter release, and aberrations in dendritic arbour morphogenesis.

Thus, Myoclonin 1/ EFHC1 is a regulator of cell division and neuronal migration during cortical development synaptic bouton and dendritic morphogenesis. Disruption of these properties lead to JME, being now therefore considered as a developmental disease.