Ninein is a centrosome protein that has been implicated in microtubule anchorage and centrosome cohesion. Mutations in the human gene have been linked to Seckel syndrome and to a rare form of skeletal dysplasia. However, the role of ninein in skeletal development remains unknown. Here, we describe a ninein knockout mouse with advanced endochondral ossification during embryonic development. Although the long bones maintain a regular size, the absence of ninein delays the formation of the bone marrow cavity in the prenatal tibia. Likewise, intramembranous ossification in the skull is more developed, leading to a premature closure of the interfrontal suture. We demonstrate that ninein is strongly expressed in osteoclasts of control mice, and that its absence reduces the fusion of precursor cells into syncytial osteoclasts, whereas the number of osteoblasts remains unaffected. As a consequence, ninein-deficient osteoclasts have a reduced capacity to resorb bone. At the cellular level, the absence of ninein interferes with centrosomal microtubule organization, reduces centrosome cohesion, and provokes the loss of centrosome clustering in multinucleated mature osteoclasts. We propose that centrosomal ninein is important for osteoclast fusion, to enable a functional balance between bone-forming osteoblasts and bone-resorbing osteoclasts during skeletal development.
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http://dx.doi.org/10.7554/eLife.93457 | DOI Listing |
Elife
June 2024
Molecular, Cellular and Developmental Biology, Centre de Biologie Intégrative, UMR5077, CNRS & Université Paul Sabatier, Toulouse, France.
Ninein is a centrosome protein that has been implicated in microtubule anchorage and centrosome cohesion. Mutations in the human gene have been linked to Seckel syndrome and to a rare form of skeletal dysplasia. However, the role of ninein in skeletal development remains unknown.
View Article and Find Full Text PDFJ Cell Biol
May 2016
Department of Neurobiology and Anatomy, Drexel University College of Medicine, Philadelphia, PA 19129
Contemporary models for neuronal migration are grounded in the view that virtually all functionally relevant microtubules (MTs) in migrating neurons are attached to the centrosome, which occupies a position between the nucleus and a short leading process. It is assumed that MTs do not undergo independent movements but rather transduce forces that enable movements of the centrosome and nucleus. The present results demonstrate that although this is mostly true, a small fraction of the MTs are centrosome-unattached, and this permits limited sliding of MTs.
View Article and Find Full Text PDFDevelopment
January 2016
IGBMC - CNRS UMR 7104 - INSERM U964 - Université de Strasbourg, 1 rue Laurent Fries, BP 10142, Illkirch 67404, Cedex, France Institut de Biologie Paris Seine, IBPS FR3631, Université Pierre et Marie Curie, 7-9 Quai Saint Bernard, Paris 75005, France
C. elegans embryonic elongation is a morphogenetic event driven by actomyosin contractility and muscle-induced tension transmitted through hemidesmosomes. A role for the microtubule cytoskeleton has also been proposed, but its contribution remains poorly characterized.
View Article and Find Full Text PDFJ Biol Chem
October 2013
From the Departments of Genetic Medicine and.
The primary cilium is required for Hedgehog signaling. So far, all known ciliogenic proteins regulate Hedgehog signaling through their role in ciliogenesis. Here we show that the mouse DZIP1 regulates Hedgehog signaling through two mechanisms.
View Article and Find Full Text PDFCell Death Dis
April 2013
Department of Molecular Pathobiochemistry, Gifu University Graduate School of Medicine, 1-1 Yanagido, Gifu, Japan.
Mitotic catastrophe, which refers to cell death or its prologue triggered by aberrant mitosis, can be induced by a heterogeneous group of stimuli, including chromosome damage or perturbation of the mitotic apparatus. We investigated the mechanism of mitotic catastrophe and cell death induced by depletion of centrosomal proteins that perturbs microtubule organization. We transfected cells harboring wild-type or mutated p53 with siRNAs targeting Aurora A, ninein, TOG, TACC3, γ-tubulin, or pericentriolar material-1, and monitored the effects on cell death.
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