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Publication : Foxg1 bimodally tunes L1-mRNA and -DNA dynamics in the developing murine neocortex.

First Author  Liuzzi G Year  2024
Journal  Development Volume  151
Issue  10 PubMed ID  38655654
Mgi Jnum  J:349015 Mgi Id  MGI:7646797
Doi  10.1242/dev.202292 Citation  Liuzzi G, et al. (2024) Foxg1 bimodally tunes L1-mRNA and -DNA dynamics in the developing murine neocortex. Development 151(10):dev202292
abstractText  Foxg1 masters telencephalic development via a pleiotropic control over its progression. Expressed within the central nervous system (CNS), L1 retrotransposons are implicated in progression of its histogenesis and tuning of its genomic plasticity. Foxg1 represses gene transcription, and L1 elements share putative Foxg1-binding motifs, suggesting the former might limit telencephalic expression (and activity) of the latter. We tested such a prediction, in vivo as well as in engineered primary neural cultures, using loss- and gain-of-function approaches. We found that Foxg1-dependent, transcriptional L1 repression specifically occurs in neopallial neuronogenic progenitors and post-mitotic neurons, where it is supported by specific changes in the L1 epigenetic landscape. Unexpectedly, we discovered that Foxg1 physically interacts with L1-mRNA and positively regulates neonatal neopallium L1-DNA content, antagonizing the retrotranscription-suppressing activity exerted by Mov10 and Ddx39a helicases. To the best of our knowledge, Foxg1 represents the first CNS patterning gene acting as a bimodal retrotransposon modulator, limiting transcription of L1 elements and promoting their amplification, within a specific domain of the developing mouse brain.
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