title: Untwisting the Caenorhabditis elegans embryo.
abstract: The nematode Caenorhabditis elegans possesses a simple embryonic nervous system with few enough neurons that the growth of each cell could be followed to provide a systems-level view of development. However, studies of single cell development have largely been conducted in fixed or pre-twitching live embryos, because of technical difficulties associated with embryo movement in late embryogenesis. We present open-source untwisting and annotation software (http://mipav.cit.nih.gov/plugin_jws/mipav_worm_plugin.php) that allows the investigation of neurodevelopmental events in late embryogenesis and apply it to track the 3D positions of seam cell nuclei, neurons, and neurites in multiple elongating embryos. We also provide a tutorial describing how to use the software (Supplementary file 1) and a detailed description of the untwisting algorithm (Appendix). The detailed positional information we obtained enabled us to develop a composite model showing movement of these cells and neurites in an 'average' worm embryo. The untwisting and cell tracking capabilities of our method provide a foundation on which to catalog C. elegans neurodevelopment, allowing interrogation of developmental events in previously inaccessible periods of embryogenesis.
authors.affiliation: Section on High Resolution Optical Imaging, National Institute of Biomedical Imaging and Bioengineering, National Institutes of Health, Bethesda, United States.
authors.forename: Ryan Patrick
authors.initials: RP
authors.lastname: Christensen
authors.affiliation: Biomedical Imaging Research Services Section, Center for Information Technology, National Institutes of Health, Bethesda, United States.
authors.forename: Alexandra
authors.initials: A
authors.lastname: Bokinsky
authors.affiliation: Developmental Biology Program, Sloan-Kettering Institute, New York, United States.
authors.forename: Anthony
authors.initials: A
authors.lastname: Santella
authors.affiliation: Section on High Resolution Optical Imaging, National Institute of Biomedical Imaging and Bioengineering, National Institutes of Health, Bethesda, United States.
authors.forename: Yicong
authors.initials: Y
authors.lastname: Wu
authors.affiliation: Program in Cellular Neuroscience, Neurodegeneration and Repair, Department of Cell Biology, Yale University School of Medicine, New Haven, United States.
authors.forename: Javier
authors.initials: J
authors.lastname: Marquina-Solis
authors.affiliation: Section on High Resolution Optical Imaging, National Institute of Biomedical Imaging and Bioengineering, National Institutes of Health, Bethesda, United States.|State Key Laboratory of Modern Optical Instrumentation, College of Optical Science and Engineering, Zhejiang University, Hangzhou, China.
authors.forename: Min
authors.initials: M
authors.lastname: Guo
authors.affiliation: Developmental Biology Program, Sloan-Kettering Institute, New York, United States.
authors.forename: Ismar
authors.initials: I
authors.lastname: Kovacevic
authors.affiliation: Section on High Resolution Optical Imaging, National Institute of Biomedical Imaging and Bioengineering, National Institutes of Health, Bethesda, United States.|Program in Cellular Neuroscience, Neurodegeneration and Repair, Department of Cell Biology, Yale University School of Medicine, New Haven, United States.
authors.forename: Abhishek
authors.initials: A
authors.lastname: Kumar
authors.affiliation: Section on High Resolution Optical Imaging, National Institute of Biomedical Imaging and Bioengineering, National Institutes of Health, Bethesda, United States.
authors.forename: Peter W
authors.initials: PW
authors.lastname: Winter
authors.affiliation: Section on High Resolution Optical Imaging, National Institute of Biomedical Imaging and Bioengineering, National Institutes of Health, Bethesda, United States.
authors.forename: Nicole
authors.initials: N
authors.lastname: Tashakkori
authors.affiliation: Biomedical Imaging Research Services Section, Center for Information Technology, National Institutes of Health, Bethesda, United States.
authors.forename: Evan
authors.initials: E
authors.lastname: McCreedy
authors.affiliation: State Key Laboratory of Modern Optical Instrumentation, College of Optical Science and Engineering, Zhejiang University, Hangzhou, China.
authors.forename: Huafeng
authors.initials: H
authors.lastname: Liu
authors.affiliation: Biomedical Imaging Research Services Section, Center for Information Technology, National Institutes of Health, Bethesda, United States.
authors.forename: Matthew
authors.initials: M
authors.lastname: McAuliffe
authors.affiliation: Department of Genetics and Developmental Biology, University of Connecticut Health Center, Farmington, United States.
authors.forename: William
authors.initials: W
authors.lastname: Mohler
authors.affiliation: Program in Cellular Neuroscience, Neurodegeneration and Repair, Department of Cell Biology, Yale University School of Medicine, New Haven, United States.
authors.forename: Daniel A
authors.initials: DA
authors.lastname: Colón-Ramos
authors.affiliation: Developmental Biology Program, Sloan-Kettering Institute, New York, United States.
authors.forename: Zhirong
authors.initials: Z
authors.lastname: Bao
authors.affiliation: Section on High Resolution Optical Imaging, National Institute of Biomedical Imaging and Bioengineering, National Institutes of Health, Bethesda, United States.
authors.forename: Hari
authors.initials: H
authors.lastname: Shroff
mesh_terms: D000818:Animals; D017173:Caenorhabditis elegans / Q000196:embryology* / Q000502:physiology*; D058948:Cell Tracking / Q000379:methods; D019295:Computational Biology / Q000379:methods*; D066289:Data Curation; D009420:Nervous System / Q000166:cytology* / Q000196:embryology*; D009474:Neurons / Q000502:physiology*; D012984:Software
keywords: C. elegans; C.elegans embryo untwisting; computational biology; developmental biology; embryonic morphogenesis; embryonic neurodevelopment; light sheet microscopy; stem cells; systems biology