A human tissue screen identifies a regulator of ER secretion as a brain-size determinant

• DOI: 10.1126/science.abb5390
• Publication Date: 2020-10-29T23:10:10Z
• Authors: Christopher Esk; Dominik Lindenhofer; Simon Haendeler; Roelof A. Wester; Florian Pflug; Benoit Schroeder; Joshua A. Bagley; Ulrich Elling; Johannes Zuber; Arndt von Haeseler; Jürgen A. Knoblich
• Keywords: Microcephaly; Genetic screen; Organoid; Human brain

Functional screen for microcephaly genes Genetic screens are widely used to identify regulators in biological processes. Human currently limited two-dimensional cell cultures, which lack the ability score tissue-dependent gene function. Esk et al. combined CRISPR-Cas9 screening with barcoded cellular lineage tracing enable loss-of-function three-dimensional human cerebral organoid tissue. By testing candidate genes, endoplasmic reticulum was found control extracellular matrix protein secretion regulating tissue integrity and brain size. This genetic implicates multiple pathways provides a tool systematic of organoids. Science , this issue p. 935