Centrosome Amplification Increases Single-Cell Branching in Post-mitotic Cells

Abstract

Centrosome amplification is a hallmark of cancer, although we are still far from understanding how this process affects tumorigenesis [1, 2]. Besides the contribution of supernumerary centrosomes to mitotic defects, their biological effects in the post-mitotic cell are not well known. Here, we exploit the effects of centrosome amplification in post-mitotic cells during single-cell branching. We show that Drosophila tracheal cells with extra centrosomes branch more than wild-type cells. We found that mutations in Rca1 and CycA affect subcellular branching, causing tracheal tip cells to form more than one subcellular lumen. We show that Rca1 and CycA post-mitotic cells have supernumerary centrosomes and that other mutant conditions that increase centrosome number also show excess of subcellular lumen branching. Furthermore, we show that de novo lumen formation is impaired in mutant embryos with fewer centrioles. The data presented here define a requirement for the centrosome as a microtubule-organizing center (MTOC) for the initiation of subcellular lumen formation. We propose that centrosomes are necessary to drive subcellular lumen formation. In addition, centrosome amplification increases single-cell branching, a process parallel to capillary sprouting in blood vessels [3]. These results shed new light on how centrosomes can contribute to pathology independently of mitotic defects.S.J.A. is a Ramon y Cajal Researcher (RYC-2007-00417); D.R. is the recipient of an FPU PhD fellowship from the Spanish Ministerio de Educación (FPU12/O5765); M.D. was supported by the Erasmus Programme. This work was supported by the Generalitat de Catalunya and grants from the Spanish Ministerio de Ciencia e Innovación/Ministerio de Economia y Competitividad (BFU2009-07629 and BFU2012-32115). IRB Barcelona is the recipient of a Severo Ochoa Award of Excellence from MINECO (Spanish Government).Peer Reviewe