Developmental biology - Organ Development|
Cilia Help Shape Size of Organs
Cilia act like tiny antennae, putting the brakes on cell division until the right growth signals appear...
Scientist have cast new light on the behavior of tiny hair-like structures called cilia found on almost every cell in the body. Cilia play important roles in human development and disease. Akin to tiny antennae, they act as cell timers arresting cell division until the right growth signals are received.
Malfunction in cilia lead to many human diseases such as polycystic kidney disease and some cancers.
Cilia are important in embryo development helpingshape the size of organs, like our brains and lungs. In adults, both loss and hyperactivity in these crucial signalling centers is implicated in cancer cell proliferation and migration.
In a study published in Developmental Cell, researchers from the Universities of Edinburgh and Lancaster developed a multi-component fluorescent biosensor that allows users to simultaneously 'light up' both cilia and cells while in the process of actively dividing.
Cellular machinery driving growth of cilia is shared during cell division.
According to Pleasantine Mill, PhD in the Human Genetics Unit, MRC Institute of Genetics & Molecular Medicine, University of Edinburgh, Western General Hospital, UK: "This powerful new tool [the fluorescent biosensor] will allow us to investigate cilia function in human disease in unprecedented detail."
The new biosensor will allow researchers to carry out studies exploring how changes in cilia length and dynamics affect the speed of cell division and tissue development in general. Matthew Ford PhD, MRC Institute of Genetics & Molecular Medicine, University of Edinburgh, UK and joint first author adds: "This new resource will shed light at an individual cell level on the interplay between the cilia and cell cycles in development, regeneration and disease." It is hoped these studies will help researchers build a more detailed picture of cilia in human disease and help monitor novel therapeutic approaches.
"It has long been known that the cilia and cell cycles are closely linked. But until now, it has been difficult to imagine these processes in parallel."
Richard Mort PhD, Division of Biomedical and Life Sciences, Faculty of Health and Medicine, Lancaster University, Lancaster, UK
• Arl13bCerulean-Fucci2a biosensor labels the cell and cilia cycles
• Analysis of cells and mice reveals persistence of cilia after the G1/S transition
• Inducible mouse line allows lineage tracing and ex vivo live imaging
• Organisms can tolerate artificially lengthened cilia without overt phenotypes.
The cilia and cell cycles are inextricably linked. Centrioles in the basal body of cilia nucleate the ciliary axoneme and sequester pericentriolar matrix (PCM) at the centrosome to organize the mitotic spindle. Cilia themselves respond to growth signals, prompting cilia resorption and cell cycle re-entry. We describe a fluorescent cilia and cell cycle biosensor allowing live imaging of cell cycle progression and cilia assembly and disassembly kinetics in cells and inducible mice. We define assembly and disassembly in relation to cell cycle stage with single-cell resolution and explore the intercellular heterogeneity in cilia kinetics. In all cells and tissues analyzed, we observed cilia that persist through the G1/S transition and into S/G2/M-phase. We conclude that persistence of cilia after the G1/S transition is a general property. This resource will shed light at an individual cell level on the interplay between the cilia and cell cycles in development, regeneration, and disease.
Matthew J. Ford, Patricia L. Yeyati, Girish R. Mali, Margaret A. Keighren, Scott H. Waddell, Heidi K. Mjoseng, Adam T. Douglas, Emma A. Hall, Asako Sakaue-Sawano, Atsushi Miyawaki, Richard R. Meehan, Luke Boulter,Ian J. Jackson, Pleasantine Mill and Richard L. Mort.
The authors are grateful to Joe Mee and the Scottish Center for Regenerative Medicine Transgenic Service for ES cell targeting; Fiona Kilanowski and Julia Dorin for ES cell karyotyping; the IGMM Advanced Imaging Resource for imaging support; and Elisabeth Freyer for help and advice on FACS analysis. The work was supported by core funding from the Medical Research Council (MC_PC_U127527200 to M.J.F., M.A.K., I.J.J., and R.L.M.; MC_UU_12018/26 to P.L.Y., G.R.M., S.H.W., E.A.H., and P.M.; MC_PC_U127574433 to R.R.M. and H.K.M.) and to R.L.M. and I.J.J. by the NC3Rs (NC/M001091/1)..
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Nov 27, 2018 Fetal Timeline Maternal Timeline News News Archive
Cilia are microtubule cell projections that come in motile and non-motile forms. They sense key mechanical and environmental cues including mitogenic signals that include Hedgehog (HH), insulin-like growth factor 1 (IGF-1), and platelet-derived growth factor (PDGF). Defects in cilia result in a broad group of disorders termed ciliopathies. Credit: Authors and Developmental Cell.