The basal position of nuclei is one pre-requisite for asymmetric cell divisions in the early mouse embryo

Anna Ajduk,Sourima Biswas Shivhare,Magdalena Zernicka-Goetz

doi:10.1016/j.ydbio.2014.05.009

Abstract

The early mouse embryo undertakes two types of cell division: symmetric that gives rise to the trophectoderm and then placenta or asymmetric that gives rise to inner cells that generate the embryo proper. Although cell division orientation is important, the mechanism regulating it has remained unclear. Here, we identify the relationship between the plane of cell division and the position of the nucleus and go towards identifying the mechanism behind it. We first find that as the 8-cell embryo progresses through the cell cycle, the nuclei of most – but not all – cells move from apical to more basal positions, in a microtubule- and kinesin-dependent manner. We then find that all asymmetric divisions happen when nuclei are located basally and, in contrast, all cells, in which nuclei remain apical, divide symmetrically. To understand the potential mechanism behind this, we determine the effects of modulating expression of Cdx2, a transcription factor key for trophectoderm formation and cell polarity. We find that increased expression of Cdx2 leads to an increase in a number of apical nuclei, whereas down-regulation of Cdx2 leads to more nuclei moving basally, which explains a previously identified relationship between Cdx2 and cell division orientation. Finally, we show that down-regulation of aPKC, involved in cell polarity, decreases the number of apical nuclei and doubles the number of asymmetric divisions. These results suggest a model in which the mutual interdependence of Cdx2 and cell polarity affects the cytoskeleton-dependent positioning of nuclei and, in consequence, the plane of cell division in the early mouse embryo.

Highlights

Division from the 8 to 16 cell stage leads to segregation of progenitors for two distinct lineages: outer cells that give rise to the extra-embryonic trophectoderm contributing to the placenta, and inner cells that give rise to the inner cell mass (ICM) contributing to the embryo proper
The alternative model suggests that cell fate is determined by cell polarity that is established along the apical–basal axis (Johnson and Ziomek, 1981b)
In order to gain insight into the mechanism regulating the plane of cell division in the early mouse embryo, we first wished to determine the events preceding symmetric vs. asymmetric divisions at the 8-cell stage

Summary

Introduction

Division from the 8 to 16 cell stage leads to segregation of progenitors for two distinct lineages: outer cells that give rise to the extra-embryonic trophectoderm contributing to the placenta, and inner cells that give rise to the inner cell mass (ICM) contributing to the embryo proper. As blastomeres with nuclei located baso-centrally prior to the NEBD may divide either asymmetrically or symmetrically, we examined whether plane of the division is determined by the pattern of the nuclear movement. Nuclei that moved to the baso-central location from an initial apical position and nuclei that maintained their baso-central position throughout the 8-cell stage were able to divide either symmetrically or asymmetrically.

Results

Conclusion