Oriented cell division in vertebrate embryogenesis

https://doi.org/10.1016/j.ceb.2011.09.009Get rights and content

Tissue morphogenesis depends on the spatial arrangement of cells during development. A number of mechanisms have been described to contribute to the final shape of a tissue or organ, ranging from cell intercalation to the response of cells to chemotactic cues. One such mechanism is oriented cell division. Oriented cell division is determined by the position of the mitotic spindle. Indeed, there is increasing evidence implicating spindle misorientation in tissue and organ misshaping, which underlies disease conditions such as tumorigenesis or polycystic kidneys. Here we review recent studies addressing how the direction of tissue growth is determined by the orientation of cell division and how both extrinsic and intrinsic cues control the position of the mitotic spindle.

Introduction

Extensive work has been done to understand how the orientation of the mitotic spindle needs to be coordinated with the asymmetric localization of cell fate determinants to ensure their asymmetric inheritance and, therefore, to determine the different fates of the daughter cells (for reviews on asymmetric cell division see [1, 2, 3, 4]). However, only in recent years, oriented cell division has emerged as an important mechanism that controls not only cell fate but also the shape and size of tissues and organs.

Here, we first review recent developmental studies on the role of oriented cell division in early vertebrate body plan specification and tissue morphogenesis. In many instances, cell division orientation is regulated by the planar cell polarity (PCP) pathway. We describe our current understanding of the mechanisms by which the PCP pathway regulates the orientation of cell division in a growing tissue.

Secondly, we consider the respective roles of cell shape and cell polarity cues for spindle orientation. We describe recent evidence arguing against a simple role for cell shape elongation in determining the position of the mitotic spindle. These data suggest that the local cortical distribution of molecules involved in cell adhesion, actin polymerization and microtubule stabilization are able to guide spindle orientation and therefore determine the position of the daughter cells.

Finally, we discuss the correlation between perturbed oriented cell division and the development of some human diseases.

Section snippets

Oriented cell division and tissue morphogenesis

Oriented cell division has been proposed to be a fundamental mechanism by which the shape of proliferating and growing tissues can be determined. Indeed, oriented cell divisions have been implicated in the correct shaping of tissues in many vertebrate developmental systems, including elongation of the primitive streak in the chick embryo [5], and development of the kidney and elongation of the fore-stomach, both in mouse embryos [6, 7]. In the zebrafish embryo, studies of oriented cell division

Cortical cues that guide the spindle position

Signaling pathways are not the only mechanism that dividing cells use to orient the mitotic spindle. According to the rule of Sachs and Hertwig, the axis of the spindle typically lies in the longest axis of the cell [33, 34]. This has been observed in a variety of systems, including normal rat kidney cells (NRK). In these cells, the spindle is preferably oriented along the long axis of the cell [35]. When cell shapes were mechanically deformed, spindles rotated and relocated along the new long

Oriented cell division and diseases

Disruption of the mitotic plane might cause organ malformation that lead to diseases such as tumorigenesis or polycystic kidney disease [5, 6, 7, 48]. Recent studies have demonstrated that the PCP pathway is required for normal kidney development, and suggest that defective PCP can lead to polycystic kidney disease (PKD). Analysis of cells in mitosis showed that during the formation of the nephrons, cells divide along the elongation of the tube and defective PCP signaling leads to randomization

Future perspectives

Oriented cell division is emerging as an important mechanism to control tissue morphogenesis and integrity. The extrinsic and intrinsic cues responsible for polarized divisions are now being identified by studies in cultured cells as well as at the tissue-level morphogenesis in vivo. There is, therefore, an increased need to integrate the knowledge acquired in single cells on the control of mitotic spindle positioning in the context of tissue or organ morphogenesis.

It seems that the PCP pathway

References and recommended reading

Papers of particular interest, published within the period of review, have been highlighted as:

  • • of special interest

  • •• of outstanding interest

Acknowledgements

This work was supported by the Swiss National Science Foundation, grants from the Swiss SystemsX.ch initiative, and LipidX-2008/011, and by an ERC advanced investigator grant to MG-G.

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