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However, the detailed and unbiased phenotypic assessment of altered embryonic development remains a challenge. Here, we explore how deep learning (U-Net) can automate segmentation tasks in various imaging modalities, and we quantify phenotypes of altered renal, neural and craniofacial development in Xenopus embryos in comparison with normal variability. We demonstrate the utility of this approach in embryos with polycystic kidneys (pkd1 and pkd2) and craniofacial dysmorphia (six1). We highlight how in toto light-sheet microscopy facilitates accurate reconstruction of brain and craniofacial structures within X. tropicalis embryos upon dyrk1a and six1 loss of function or treatment with retinoic acid inhibitors. These tools increase the sensitivity and throughput of evaluating developmental malformations caused by chemical or genetic disruption. Furthermore, we provide a library of pre-trained networks and detailed instructions for applying deep learning to the reader's own datasets. We demonstrate the versatility, precision and scalability of deep neural network phenotyping on embryonic disease models. By combining light-sheet microscopy and deep learning, we provide a framework for higher-throughput characterization of embryonic model organisms.<\/jats:p>\n               <jats:p>This article has an associated \u2018The people behind the papers\u2019 interview.<\/jats:p>","DOI":"10.1242\/dev.199664","type":"journal-article","created":{"date-parts":[[2021,11,5]],"date-time":"2021-11-05T11:54:07Z","timestamp":1636113247000},"source":"Crossref","is-referenced-by-count":37,"title":["Deep learning is widely applicable to phenotyping embryonic development and disease"],"prefix":"10.1242","volume":"148","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3543-2519","authenticated-orcid":false,"given":"Thomas","family":"Naert","sequence":"first","affiliation":[{"name":"Institute of Anatomy, University of Zurich, Zurich 8057, Switzerland; Swiss National Centre of Competence in Research (NCCR) Kidney Control of Homeostasis (Kidney.CH), Zurich 8057, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"\u00d6zg\u00fcn","family":"\u00c7i\u00e7ek","sequence":"additional","affiliation":[{"name":"Department of Computer Science, Albert-Ludwigs-University, Freiburg 79100, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paulina","family":"Ogar","sequence":"additional","affiliation":[{"name":"Institute of Anatomy, University of Zurich, Zurich 8057, Switzerland; Swiss National Centre of Competence in Research (NCCR) Kidney Control of Homeostasis (Kidney.CH), Zurich 8057, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Max","family":"B\u00fcrgi","sequence":"additional","affiliation":[{"name":"Institute of Anatomy, University of Zurich, Zurich 8057, Switzerland; Swiss National Centre of Competence in Research (NCCR) Kidney Control of Homeostasis (Kidney.CH), Zurich 8057, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nikko-Ideen","family":"Shaidani","sequence":"additional","affiliation":[{"name":"National Xenopus Resource and Eugene Bell Center for Regenerative Biology and Tissue Engineering, Marine Biological Laboratory, Woods Hole, MA 02543, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0429-7027","authenticated-orcid":false,"given":"Michael M.","family":"Kaminski","sequence":"additional","affiliation":[{"name":"Berlin Institute for Medical Systems Biology, Max Delbr\u00fcck Center for Molecular Medicine in the Helmholtz Association, Berlin 10115, Germany"},{"name":"Department of Nephrology and Medical Intensive Care, Charit\u00e9 Universit\u00e4tsmedizin Berlin, Berlin 10117, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuxiao","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Psychiatry and Behavioral Sciences, UCSF Weill Institute for Neurosciences, University of California, San Francisco, CA 94158, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kelli","family":"Grand","sequence":"additional","affiliation":[{"name":"Institute of Anatomy, University of Zurich, Zurich 8057, Switzerland; Swiss National Centre of Competence in Research (NCCR) Kidney Control of Homeostasis (Kidney.CH), Zurich 8057, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marko","family":"Vujanovic","sequence":"additional","affiliation":[{"name":"Institute of Anatomy, University of Zurich, Zurich 8057, Switzerland; Swiss National Centre of Competence in Research (NCCR) Kidney Control of Homeostasis (Kidney.CH), Zurich 8057, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel","family":"Prata","sequence":"additional","affiliation":[{"name":"Institute of Anatomy, University of Zurich, Zurich 8057, Switzerland; Swiss National Centre of Competence in Research (NCCR) Kidney Control of Homeostasis (Kidney.CH), Zurich 8057, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Friedhelm","family":"Hildebrandt","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Boston Children's Hospital, Harvard Medical School, Boston, MA 02115,USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"Brox","sequence":"additional","affiliation":[{"name":"Department of Computer Science, Albert-Ludwigs-University, Freiburg 79100, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Olaf","family":"Ronneberger","sequence":"additional","affiliation":[{"name":"Department of Computer Science, Albert-Ludwigs-University, Freiburg 79100, Germany"},{"name":"BIOSS Centre for Biological Signalling Studies, Albert-Ludwigs-University, Freiburg, Germany"},{"name":"DeepMind, London WC2H 8AG , UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fabian F.","family":"Voigt","sequence":"additional","affiliation":[{"name":"Laboratory of Neural Circuit Dynamics, Brain Research Institute, University of Zurich, Zurich 8057, Switzerland; Neuroscience Center Zurich, Zurich 8057, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fritjof","family":"Helmchen","sequence":"additional","affiliation":[{"name":"Laboratory of Neural Circuit Dynamics, Brain Research Institute, University of Zurich, Zurich 8057, Switzerland; Neuroscience Center Zurich, Zurich 8057, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Johannes","family":"Loffing","sequence":"additional","affiliation":[{"name":"Institute of Anatomy, University of Zurich, Zurich 8057, Switzerland; Swiss National Centre of Competence in Research (NCCR) Kidney Control of Homeostasis (Kidney.CH), Zurich 8057, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marko E.","family":"Horb","sequence":"additional","affiliation":[{"name":"National Xenopus Resource and Eugene Bell Center for Regenerative Biology and Tissue Engineering, Marine Biological Laboratory, Woods Hole, MA 02543, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8404-3291","authenticated-orcid":false,"given":"Helen Rankin","family":"Willsey","sequence":"additional","affiliation":[{"name":"Department of Psychiatry and Behavioral Sciences, UCSF Weill Institute for Neurosciences, University of California, San Francisco, CA 94158, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2963-6865","authenticated-orcid":false,"given":"Soeren S.","family":"Lienkamp","sequence":"additional","affiliation":[{"name":"Institute of Anatomy, University of Zurich, Zurich 8057, Switzerland; 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