Adult brain neurogenesis
Elongator is a multiprotein complex composed of 6 subunits (Elp1-6), which is expressed both in the nucleus and cytoplasm where its Elp3 acts as enzyme modificator. In the nucleus, it promotes transcriptional elongation and paternal genome demethylation, and in the cytoplasm, it contributes to exocytosis and tRNA modifications. EU funded 'Defining the functions of Elongator in adult brain neurogenesis' (FAN) project to investigate whether elongator contributes to neurogenesis in the adult brain and to characterize its acetylation targets. Firstly, researchers demonstrated expression of the Elp subunits in micro-dissected postnatal mouse brain zones which retain stem cells. They also found that knockout Flp3 animals die before postnatal day 23. The size of the brain and, in particular, the thickness of the cortical plate was reduced upon Elp3 deletion, and knockout animals were hydrocephales. Epithelia like cells involved in the production of cerebrospinal fluid, ependymal cells, are polarized through a multi-step process by primary cilia in radial glia and then refined by motile cilia in ependymal cells. Researchers showed that both polarities were impaired upon Elp3 deletion. Finally they compared acetylome from Elp3 knockout and WT cortices in global analysis approach to indentifiy new proteins acetylated by Elp3. Among the candidates they found CEP290, a protein which mutations have been implicated in many autosomal disorders including early-onset retinal degeneration. In conclusion, this study demonstrated for the first time the involvement of Elongator complex in ciliogenesis. Results of the project also pointed to a broader function of Elongator in different ciliated organs.
Keywords
Adult brain, stem cells, neurogenesis, Elongator, ependymal cells.
