Zygotic development without functional mitotic centrosomes

The centrosome is the dominant microtubule-organizing center in animal cells. At the onset of mitosis, each cell normally has two centrosomes that lie on opposite sides of the nucleus. Centrosomes nucleate the growth of microtubules and orchestrate the efficient assembly of the mitotic spindle. Recent studies in vivo and in vitro have shown that the spindle can form even in the absence of centrosomes and demonstrate that individual cells can divide without this organelle. However, since centrosomes are involved in multiple processes in vivo, including polarized cell divisions, which are an essential developmental mechanism for producing differentiated cell types, it remains to be shown whether or not a complete organism can develop without centrosomes. Here we show that in Drosophila a centrosomin (cnn) null mutant, which fails to assemble fully functional mitotic centrosomes and has few or no detectable astral microtubules, can develop into an adult fly. These results challenge long-held assumptions that the centrosome and the astral microtubules emanating from it are essential for development and are required specifically for spindle orientation during asymmetric cell divisions.

[1]  C. Sunkel,et al.  Gamma‐tubulin is required for the structure and function of the microtubule organizing centre in Drosophila neuroblasts. , 1995, The EMBO journal.

[2]  Y. Jan,et al.  Polarity in Cell Division What Frames Thy Fearful Asymmetry? , 2000, Cell.

[3]  T. Kaufman,et al.  The centrosomin protein is required for centrosome assembly and function during cleavage in Drosophila. , 1999, Development.

[4]  P. G. Wilson,et al.  Monastral bipolar spindles: implications for dynamic centrosome organization. , 1997, Journal of cell science.

[5]  Eric Karsenti,et al.  Self-organization of microtubules into bipolar spindles around artificial chromosomes in Xenopus egg extracts , 1996, Nature.

[6]  E. Schiebel gamma-tubulin complexes: binding to the centrosome, regulation and microtubule nucleation. , 2000, Current opinion in cell biology.

[7]  S. Strome Determination of cleavage planes , 1993, Cell.

[8]  Yixian Zheng,et al.  Nucleation of microtubule assembly by a γ-tubulin-containing ring complex , 1995, Nature.

[9]  W. Sullivan,et al.  Spindle Assembly and Mitosis without Centrosomes in Parthenogenetic Sciara Embryos , 1998, The Journal of cell biology.

[10]  M. Snyder,et al.  A highly divergent gamma-tubulin gene is essential for cell growth and proper microtubule organization in Saccharomyces cerevisiae , 1995, The Journal of cell biology.

[11]  S. Strome,et al.  Cleavage Plane Specification in C. elegans: How to Divide the Spoils , 1996, Cell.

[12]  C. Rieder,et al.  The Sudden Recruitment of γ-Tubulin to the Centrosome at the Onset of Mitosis and Its Dynamic Exchange Throughout the Cell Cycle, Do Not Require Microtubules , 1999, The Journal of cell biology.

[13]  E. Schejter,et al.  Mutations in centrosomin reveal requirements for centrosomal function during early Drosophila embryogenesis , 1999, Current Biology.

[14]  J. C. Clemens,et al.  Use of double-stranded RNA interference in Drosophila cell lines to dissect signal transduction pathways. , 2000, Proceedings of the National Academy of Sciences of the United States of America.

[15]  A. Mccarthy Development , 1996, Current Opinion in Neurobiology.

[16]  R. Balczon The centrosome in animal cells and its functional homologs in plant and yeast cells. , 1996, International review of cytology.

[17]  Eric Karsenti,et al.  Spindle Assembly in Xenopus Egg Extracts: Respective Roles of Centrosomes and Microtubule Self-Organization , 1997, The Journal of cell biology.

[18]  Alexey Khodjakov,et al.  Centrosome-independent mitotic spindle formation in vertebrates , 2000, Current Biology.

[19]  Smruti J Vidwans,et al.  Cytoskeleton: Centrosom-in absentia , 1999, Current Biology.

[20]  J. Rossier,et al.  Basal body duplication in Paramecium requires γ-tubulin , 1999, Current Biology.

[21]  D. Agard,et al.  Gamma-tubulin complexes and microtubule nucleation. , 2001, Current opinion in structural biology.

[22]  T. Kaufman,et al.  The centrosome in Drosophila oocyte development. , 2000, Current topics in developmental biology.

[23]  M. Bownes,et al.  Drosophila: A practical approach: edited by D. B. Roberts IRL Press, 1986. £26.00/$47.00 (xix + 295 pages) ISBN 0 94746 66 7 , 1987 .

[24]  Ira Herskowitz,et al.  Mechanisms of asymmetric cell division: Two Bs or not two Bs, that is the question , 1992, Cell.

[25]  T. Hays,et al.  The microtubule motor cytoplasmic dynein is required for spindle orientation during germline cell divisions and oocyte differentiation in Drosophila. , 1997, Development.

[26]  T. Kaufman,et al.  Drosophila Centrosomin Protein is Required for Male Meiosis and Assembly of the Flagellar Axoneme , 1998, The Journal of cell biology.

[27]  B. Alberts,et al.  Microtubule nucleation by γ-tubulin-containing rings in the centrosome , 1995, Nature.

[28]  S. Bonaccorsi,et al.  Spindle assembly in Drosophila neuroblasts and ganglion mother cells , 1999, Nature Cell Biology.

[29]  G. Géraud,et al.  Polar organization of gamma-tubulin in acentriolar mitotic spindles of Drosophila melanogaster cells. , 1995, Journal of cell science.

[30]  J. Rossier,et al.  Basal body duplication in Paramecium requires gamma-tubulin. , 1999, Current biology : CB.

[31]  T. Kaufman,et al.  The Homeotic Target Gene centrosomin Encodes an Essential Centrosomal Component , 1996, Cell.

[32]  B. Oakley,et al.  γ-tubulin is a component of the spindle pole body that is essential for microtubule function in Aspergillus nidulans , 1990, Cell.