New Screening Approach Reveals Novel Regulators of Microcephaly

Researchers combine organoids, CRISPR-Cas9, and cellular barcoding technologies to identify genes that influence brain size.

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ABOVE: A cerebral organoid
© IMBA/KNOBLICH LAB

The paper
C. Esk et al., “A human tissue screen identifies a regulator of ER secretion as a brain-size determinant,” Science, 370:935–41, 2020.

Organoids can be invaluable tools for studying human disease. But they’re often difficult to work with—especially when it comes to assessing multiple candidate genes that underlie a particular condition.

Over eight years of work, Jürgen Knoblich and colleagues at the Institute of Molecular Biotechnology in Vienna have come up with a way to get around this problem. Their approach combines brain organoids with two other technologies—CRISPR-Cas9 to knock out specific genes and DNA barcoding to track individual cells and their progeny.

The researchers recently trialed their approach, dubbed CRISPR-LIneage tracing at Cellular resolution in Heterogeneous Tissue (CRISPR-LICHT), in a screen for genes linked to microcephaly, a condition in which a baby’s head is smaller than expected. The team found 13 genes with ...

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Meet the Author

  • Catherine Offord

    Catherine is a science journalist based in Barcelona.

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