title: Systems-level quantification of division timing reveals a common genetic architecture controlling asynchrony and fate asymmetry.
abstract: Coordination of cell division timing is crucial for proper cell fate specification and tissue growth. However, the differential regulation of cell division timing across or within cell types during metazoan development remains poorly understood. To elucidate the systems-level genetic architecture coordinating division timing, we performed a high-content screening for genes whose depletion produced a significant reduction in the asynchrony of division between sister cells (ADS) compared to that of wild-type during Caenorhabditis elegans embryogenesis. We quantified division timing using 3D time-lapse imaging followed by computer-aided lineage analysis. A total of 822 genes were selected for perturbation based on their conservation and known roles in development. Surprisingly, we find that cell fate determinants are not only essential for establishing fate asymmetry, but also are imperative for setting the ADS regardless of cellular context, indicating a common genetic architecture used by both cellular processes. The fate determinants demonstrate either coupled or separate regulation between the two processes. The temporal coordination appears to facilitate cell migration during fate specification or tissue growth. Our quantitative dataset with cellular resolution provides a resource for future analyses of the genetic control of spatial and temporal coordination during metazoan development.
authors.affiliation: Department of Biology, Hong Kong Baptist University, Hong Kong, China.
authors.forename: Vincy Wing Sze
authors.initials: VW
authors.lastname: Ho
authors.affiliation: Department of Biology, Hong Kong Baptist University, Hong Kong, China.
authors.forename: Ming-Kin
authors.initials: MK
authors.lastname: Wong
authors.affiliation: Department of Biology, Hong Kong Baptist University, Hong Kong, China.
authors.forename: Xiaomeng
authors.initials: X
authors.lastname: An
authors.affiliation: Department of Biology, Hong Kong Baptist University, Hong Kong, China.
authors.forename: Daogang
authors.initials: D
authors.lastname: Guan
authors.affiliation: Department of Biology, Hong Kong Baptist University, Hong Kong, China.
authors.forename: Jiaofang
authors.initials: J
authors.lastname: Shao
authors.affiliation: Department of Biology, Hong Kong Baptist University, Hong Kong, China.
authors.forename: Hon Chun Kaoru
authors.initials: HC
authors.lastname: Ng
authors.affiliation: Department of Biology, Hong Kong Baptist University, Hong Kong, China.
authors.forename: Xiaoliang
authors.initials: X
authors.lastname: Ren
authors.affiliation: Department of Biology, Hong Kong Baptist University, Hong Kong, China Center for Stem Cell and Translational Medicine, School of Life Sciences Anhui University, Hefei, China.
authors.forename: Kan
authors.initials: K
authors.lastname: He
authors.affiliation: Division of Life Science and Division of Biomedical Engineering, The Hong Kong University of Science and Technology, Hong Kong, China.
authors.forename: Jinyue
authors.initials: J
authors.lastname: Liao
authors.affiliation: Division of Life Science and Division of Biomedical Engineering, The Hong Kong University of Science and Technology, Hong Kong, China.
authors.forename: Yingjin
authors.initials: Y
authors.lastname: Ang
authors.affiliation: Department of Electronic Engineering, City University of Hong Kong, Hong Kong, China.
authors.forename: Long
authors.initials: L
authors.lastname: Chen
authors.affiliation: Department of Electronic Engineering, City University of Hong Kong, Hong Kong, China.
authors.forename: Xiaotai
authors.initials: X
authors.lastname: Huang
authors.affiliation: Department of Biology, Hong Kong Baptist University, Hong Kong, China.
authors.forename: Bin
authors.initials: B
authors.lastname: Yan
authors.affiliation: Department of Biology, Hong Kong Baptist University, Hong Kong, China.
authors.forename: Yiji
authors.initials: Y
authors.lastname: Xia
authors.affiliation: Department of Electronic Engineering, City University of Hong Kong, Hong Kong, China.
authors.forename: Leanne Lai Hang
authors.initials: LL
authors.lastname: Chan
authors.affiliation: Division of Life Science and Division of Biomedical Engineering, The Hong Kong University of Science and Technology, Hong Kong, China.
authors.forename: King Lau
authors.initials: KL
authors.lastname: Chow
authors.affiliation: Department of Electronic Engineering, City University of Hong Kong, Hong Kong, China.
authors.forename: Hong
authors.initials: H
authors.lastname: Yan
authors.affiliation: Department of Biology, Hong Kong Baptist University, Hong Kong, China State Key Laboratory of Environmental and Biological Analysis, Hong Kong Baptist University, Hong Kong, China zyzhao@hkbu.edu.hk.
authors.forename: Zhongying
authors.initials: Z
authors.lastname: Zhao
mesh_terms: D000818:Animals; D017173:Caenorhabditis elegans / Q000196:embryology / Q000235:genetics; D029742:Caenorhabditis elegans Proteins / Q000096:biosynthesis*; D002454:Cell Differentiation / Q000235:genetics*; D002455:Cell Division / Q000235:genetics*; D019070:Cell Lineage / Q000235:genetics; D002465:Cell Movement; D047108:Embryonic Development; D018507:Gene Expression Regulation, Developmental
chemical_list: D029742:Caenorhabditis elegans Proteins
keywords: C. elegans; asynchrony of cell division; automated lineaging; cell cycle length; cell division timing