Right-left asymmetry of cell proliferation predominates in mouse embryos undergoing clockwise axial rotation

Differential growth is fundamental to most mechanisms proposed for axial rotation in amniotes. Other mechanisms such as changes in cell shape are not consistently suggested by ultrastructure. Lateral asymmetries in cell proliferation exist in mouse and chick embryos undergoing normal, anticlockwise axial rotation, but there has been no investigation of inverse clockwise rotation that could test the correlation.

We used the BALB/cHu-iv/iv, situs inversus mouse to test the apparent correlation of lateral asymmetries with morphogenesis that we saw in cell division patterns of normally rotating mice. Proliferation indices were collected from tritium autoradiograms.

Asymmetry of cell proliferation in inverse axial rotation is a mirror image of the pattern seen for normal axial rotation: right predominates over left. This asymmetry is statistically significant and correlates with morphology. Patterns of proliferation in constraining extraembryonic membranes, particularly visceral yolk sac, suggest that rotation could be pushed by uneven lateral growth as body and gut tubes form, for they are attached to these membranes.

Data from iv/iv mice provide additional evidence that differential growth, constrained by contiguous extraembryonic membranes, may drive closure of body and gut walls and contribute to axial rotation. Asymmetries of cell proliferation are likely consequences of genetic cascades, and will need to be incorporated with in situ information on gene activity.