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Foxg1 bimodally tunes L1-mRNA and -DNA dynamics in the developing murine neocortex
Gabriele Liuzzi1, Osvaldo Artimagnella1, Simone Frisari1
1Laboratory of Cerebral Cortex Development, SISSA, Trieste 34136, Italy.
Development (Cambridge, England)
|April 24, 2024
Summary
Foxg1, a key gene in brain development, uniquely controls L1 retrotransposons. It represses L1 transcription while promoting its amplification in specific brain regions.
Area of Science:
- Neuroscience
- Genetics
- Molecular Biology
Background:
- Foxg1 is crucial for telencephalic development.
- L1 retrotransposons influence central nervous system (CNS) development and genomic plasticity.
- Foxg1 may regulate L1 elements due to shared binding motifs.
Purpose of the Study:
- To investigate the regulatory relationship between Foxg1 and L1 retrotransposons in the developing brain.
- To determine if Foxg1 represses L1 transcription and activity in vivo.
Main Methods:
- Utilized loss- and gain-of-function approaches in vivo and in primary neural cultures.
- Analyzed transcriptional and epigenetic regulation of L1 elements.
- Investigated physical interactions between Foxg1 and L1-mRNA.
Main Results:
- Foxg1-dependent L1 transcriptional repression occurs in specific progenitor and neuronal populations.
- Foxg1 interacts with L1-mRNA and promotes L1 DNA content in the neonatal neopallium.
- Foxg1 antagonizes the suppressive effects of Mov10 and Ddx39a helicases on retrotranscription.
Conclusions:
- Foxg1 acts as a novel bimodal regulator of L1 retrotransposons in the developing mouse brain.
- Foxg1 limits L1 transcription while simultaneously promoting L1 amplification in a specific neurodevelopmental context.
