PT - JOURNAL ARTICLE AU - David K. Breslow AU - Sascha Hoogendoorn AU - Adam R. Kopp AU - David W. Morgens AU - Brandon K. Vu AU - Kyuho Han AU - Amy Li AU - Gaelen T. Hess AU - Michael C. Bassik AU - James K. Chen AU - Maxence V. Nachury TI - A comprehensive portrait of cilia and ciliopathies from a CRISPR-based screen for Hedgehog signaling AID - 10.1101/156059 DP - 2017 Jan 01 TA - bioRxiv PG - 156059 4099 - http://biorxiv.org/content/early/2017/06/27/156059.short 4100 - http://biorxiv.org/content/early/2017/06/27/156059.full AB - The primary cilium organizes Hedgehog signaling, shapes embryonic development and is the unifying cause of the ciliopathies. We conducted a functional genomic screen for Hedgehog signaling by engineering antibiotic-based selection of Hedgehog-responsive cells and applying genome-wide CRISPR-mediated gene disruption. The screen robustly identifies factors required for ciliary signaling with few false positives or false negatives. Characterization of hit genes uncovers novel components of several ciliary structures including a protein complex containing ε- and δ- tubulin that is required for centriole maintenance. The screen also provides an unbiased tool for classifying ciliopathies and reveals that many forms of congenital heart defects are ciliopathies. Collectively, this screen enables a systematic analysis of ciliary function and of ciliopathies and also defines a versatile platform for dissecting signaling pathways through CRISPR-based screening.