MODELING THE MITOTIC APPARATUS - FROM THE DISCOVERY OF THE BIPOLAR SPINDLE TO MODERN CONCEPTS

This bibliographical review of the modelling of the mitotic apparatus covers a period of one hundred and twenty years, from the discovery of the bipolar mitotic spindle up to the present day. Without attempting to be fully comprehensive, it will describe the evolution of the main ideas that have left their mark on a century of experimental and theo retical research. Fol and Butschli's first writings date back to 1873, at a time when Schleiden and Schwann's cell theory was rapidly gainin g ground throughout Germany. Both mitosis and chromosomes were to be d iscovered within the space of thirty years, along with the two key eve nts in the animal and plant reproductive cycle, namely fecondation and meiosis. The mitotic pole, a term still in use to this day, was emplo yed to describe a morphological fact which was noted as early as 1876, namely that the lines and the dots of the karyokinetic figure, with i ts spindle and asters, looks remarkably like the lines of force around a bar magnet. This was to lead to models designed to explain the move ments of chromosomes which take place when the cell nucleus appears to cease to exist as an organelle during mitosis. The nature of those me chanisms and the origin of the forces behind the chromosomes' ordered movements were central to the debate. Auguste Prenant, in a remarkable bibliographical synthesis published in 1910, summed up the opposing v iewpoints of the 'vitalists', on the one hand, who favoured the theory of contractility or extensility in spindle fibres, and of those who b elieved in models based on physical phenomena, on the other. The latte r subdivided into two groups: some, like Butschli, Rhumbler or Leduc, referred to diffusion, osmosis and superficial tension, whilst the oth ers, led by Gallardo and Hartog, focused on the laws of electromagneti sm. Lillie, Kuwada and Darlington followed up this line of research. T he mid-2Oth century was a major turning point. Most of the modelling m entioned above was criticized and fell into disuse after disappearing from research publications and textbooks. This marked the onset of a n ew era, as electron microscopes made possible the materialization and detailed study of the macromolecular elements of the fibres, filaments and microtubules of the cytoskeleton. The successive phases of(a) de Harven and Bernhard's 1956 discovery of the centriole's ultrastructure , (b) its identification with the basal body of the cilia and flagella , confirming the theory set out by Henneguy and von Lenhossek (1898-99 ), (c) the universal presence of microtubules in animal, vegetal and e ukaryotic protist cells, (d) the polymerization-depolymerization induc ed reversible transformations of the tubulin pool in mitosing cells (I noue, 1960), (e) ultrastructural comparative studies of the mitotic ap paratus of eukaryotes illustrating the Pickett-Heaps integrating conce pt of the MTOC (microtubule-organizing centre), (f) the possibility of in vitro experiments on mtocs or on microtubules, brings us upon the present day, which has seen the focus placed on the concept of motor-p roteins (kinesin, dynein) and on cell cycle models. The latter are bas ed on a close coincidence between the observable modifications of the mitotic apparatus and the periodic variations in intracellular concent rations of calcium or of certain enzymes (cyclins, Cdc2) during the ma in transitions of the cell cycle. The potential role of biophysics in the construction of a unified mitosis theory is examined.