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PRDM16 co-operates with LHX2 to shape the human brain.
Biorxiv : the Preprint Server for Biology
|August 23, 2023
Summary
PRDM16 mutations cause developmental brain disorders like lissencephaly. This study reveals PRDM16 collaborates with LHX2 in neural stem cells, impacting cortical development.
Area of Science:
- Genetics
- Developmental Biology
- Neuroscience
Background:
- PRDM16 is a transcriptional regulator crucial for various stem cell types.
- Mutations in PRDM16 are implicated in 1p36 deletion syndrome.
- PRDM16's role in human brain development is not fully understood.
Approach:
- A patient with a de novo PRDM16 mutation, lissencephaly, and microcephaly was studied.
- Human stem cells were engineered to model the mutation, creating cortical organoids.
- RNA sequencing and ChIP-sequencing were employed to analyze molecular changes.
Key Points:
- PRDM16 mutation led to altered cell cycle dynamics and gene expression changes (cell adhesion, WNT signaling) in cortical organoids.
- PRDM16 binds to developmental gene regulatory regions in the human fetal cortex.
- A shared motif between PRDM16 and LHX2 suggests a collaborative regulatory role.
Conclusions:
- PRDM16 is essential for human cortical development, with mutations causing significant neurodevelopmental defects.
- PRDM16 and LHX2 likely partner to regulate gene expression in cortical radial glia.
- This partnership is critical for normal cortical development, highlighting a novel mechanism in neurogenesis.
