The Project

The ways in which cells set the size of intracellular structures is an important but largely unsolved problem [1]. The rapid early embryonic divisions of many embryos pose special problems in proportionally adjusting these intracellular structures to the rapidly changing cell size. Many checkpoints common in somatic cells are missing from these divisions, which are characterized by rapid reductions in cell size and short cell cycles [2]. Embryonic cells must therefore possess simple and robust mechanisms that allow the size of many of their intracellular structures to rapidly scale with cell size. Here, we study the mechanism by which one structure, the centrosome, scales in size during early embryonic divisions of C. elegans.

We show that in the early divisions, centrosome size is directly related to cell size and is independent of lineage. Two sets of experiments suggest that the total amount of maternally supplied centrosome proteins could limit centrosome size. First, the combined volume of all centrosomes formed at any one time in the developing embryo is constant. Second, the total volume of centrosome in any one cell is independent of centrosome number. By increasing the amount of centrosome proteins in the cell, we provide evidence that one component that limits centrosome size is the conserved pericentriolar material protein SPD-2 [3], which we show binds to and targets polo-like kinase 1 [3, 4] to centrosomes.

We propose a “limiting component” hypothesis for centrosome size, in which the volume of the cell sets centrosome size by limiting the total amount of centrosome components. Centrosome components in the cytoplasm are distributed proportionally to the size of the daughter cells. The total amount of available centrosomal protein then restricts the size of the centrosomes. This idea could be a general mechanism for setting the size of intracellular organelles during development.

[1] Marshall, W.F. (2004). Cellular length control systems. Annu Rev Cell Dev Biol 20, 677-693. [Download]

[2] Hyman, A.A., and Oegema, K. (2006). Cell Division, WormBook, ed. The C. elegans Research Community, WormBook. [Download]

[3] Kemp, C.A., Kopish, K.R., Zipperlen, P., Ahringer, J., and O'Connell, K.F. (2004). Centrosome maturation and duplication in C. elegans require the coiled-coil protein SPD-2. Dev Cell 6, 511-523. [Download]

[4] Barr, F., Silljé, H., and Nigg, E. (2004). Polo-like kinases and the orchestration of cell division. Nat Rev Mol Cell Biol 5, 429-441. [Download]