Abstract

During cell division, the mitotic spindle, a macromolecular structure primarily comprised of microtubules, drives chromosome alignment and partitioning between daughter cells. Mitotic spindles can sense cellular dimensions in order to adapt their length and mass to cell size. This scaling capacity is particularly remarkable during early embryo cleavage when cells divide rapidly in the absence of cell growth, thus leading to a reduction of cell volume at each division. Although mitotic spindle size scaling can occur over an order of magnitude in early embryos, in many species the duration of mitosis is relatively short, constant throughout early development and independent of cell size. Therefore, a key challenge for cells during embryo cleavage is not only to assemble a spindle of proper size, but also to do it in an appropriate time window which is compatible with embryo development. How spatial and temporal scaling of the mitotic spindle is achieved and coordinated with the duration of mitosis remains elusive. In this review, we will focus on the mechanisms that support mitotic spindle spatial and temporal scaling over a wide range of cell sizes and cellular contexts. We will present current models and propose alternative mechanisms allowing cells to spatially and temporally coordinate microtubule and mitotic spindle assembly.

Highlights

  • Metazoan development relies on biological processes that occur at very different scales, ranging from molecules to organisms, and that must be coordinated in space and time.During early embryogenesis, a succession of rapid cell divisions occurs in the absence of growth, leading to a dramatic reduction in cell size

  • Recent studies in zebrafish embryos and encapsulated or cell-free Xenopus egg extracts have functionally linked microtubule density to spindle length, and have suggested that the number of microtubules, rather than their dynamics, is the critical parameter controlling the spatial scaling of spindles with cell size [8,106]

  • The notion of “folder” mechanism was proposed to account for size changes during the successive larval stages of C. elegans

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Summary

Introduction

Metazoan development relies on biological processes that occur at very different scales, ranging from molecules to organisms, and that must be coordinated in space and time. Temporal scaling relationships would correspond to potential correlations between the duration of organelle assembly and cell cycle length. In this line, a recent study highlighted the unexpected link between nuclear size and the duration of interphase [22]. Since mitotic spindles must assemble within a relatively fixed time window limited by the duration of mitosis, understanding temporal scaling in this context is important This is especially true during the successive rapid divisions of early embryos, which must be coordinated precisely to ensure proper embryo patterning. We highlight some experimental observations that might be indicative of the physiological relevance of mitotic spindle spatial scaling and the temporal control of spindle assembly

Mitotic Spindle Assembly
Mechanisms Ensuring Spatial and Temporal Scaling of the Mitotic Spindle
Microtubule Dynamics Control Spindle Scaling in Space and in Time
Catastrophe
Growth Rate
Microtubule Nucleation Controls Spindle Mass and Length Scaling in Metaphase
Nuclear Size and Initial Spindle Length
Centrosomes and Spindle Assembly Scaling
Discussion
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