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Tet Controls Axon Guidance in Early Brain Development through Glutamatergic Signaling.

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    Biorxiv : the Preprint Server for Biology
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    Tet protein regulates early brain development in fruit flies by controlling axon guidance. It modulates glutamatergic signaling, impacting neurodevelopmental pathways and showing functional overlap with Fragile X gene.

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    Area of Science:

    • Neuroscience
    • Developmental Biology
    • Genetics

    Background:

    • Mutations in human TET proteins are linked to neurodevelopmental disorders.
    • The function of Tet in early brain development remains largely unexplored.

    Approach:

    • Investigated Tet's role in Drosophila mushroom body (MB) axon guidance.
    • Utilized transcriptomic analysis to identify downstream targets of Tet.
    • Employed CRISPR/Cas9 and RNAi to validate gene functions.
    • Examined the interaction between Tet, glutamatergic signaling, and the Fmr1 gene.

    Key Points:

    • Tet mutation causes axon guidance defects in the developing Drosophila brain.
    • Tet regulates glutamine synthetase 2 (Gs2), a key enzyme in glutamatergic signaling.
    • Tet and Gs2 function in insulin-producing cells to control MB axon guidance.
    • Tet's DNA-binding domain is crucial for its function in axon guidance.

    Conclusions:

    • Tet plays a novel role in regulating brain development and axon guidance via glutamatergic signaling.
    • Tet's function in axon guidance is conserved and may be relevant to neurodevelopmental disorders.
    • Tet and Fmr1 exhibit functional overlap in regulating brain development.