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PRDM16 co-operates with LHX2 to shape the human brain
Varun Suresh1,2,3, Bidisha Bhattacharya1,2, Rami Yair Tshuva1,2
1Department of Molecular Genetics, Weizmann Institute of Science, 234 Herzl St., Rehovot 7610001, Israel.
Oxford Open Neuroscience
|April 10, 2024
Summary
PRDM16 mutations cause developmental brain disorders like lissencephaly. This study reveals PRDM16 collaborates with LHX2 in regulating neural stem cell development.
Area of Science:
- Genetics
- Developmental Biology
- Neuroscience
Background:
- PRDM16 is a transcriptional regulator involved in various stem cell types.
- PRDM16 is implicated in 1p36 deletion syndrome, a subtelomeric microdeletion disorder.
- Mutations in PRDM16 can lead to developmental abnormalities.
Purpose of the Study:
- To investigate the role of PRDM16 in human cortical development.
- To characterize the effects of a novel PRDM16 mutation on neural stem cells.
- To identify interacting partners and regulatory pathways of PRDM16 in the brain.
Main Methods:
- Generated human stem cells with a PRDM16 nonsense mutation.
- Created and analyzed cortical organoids using RNA sequencing and ChIP-sequencing.
- Compared PRDM16 binding sites with LHX2 binding sites in human and mouse models.
Main Results:
- A patient with a de novo PRDM16 mutation presented with lissencephaly and microcephaly.
- Cortical organoids showed altered cell cycle dynamics, cell adhesion, and WNT signaling.
- PRDM16 and LHX2 share binding motifs and target common genes in cortical development.
Conclusions:
- PRDM16 plays a critical role in human cortical development.
- PRDM16 mutations can cause severe brain malformations.
- PRDM16 and LHX2 cooperate in regulating neural stem cell function and cortical development.
