Integration of Cellular Dynamics and Morphology to Understand Mouse Facial Development

Abstract

One common phenotype observed in response to many developmental perturbations is a change in proliferation or apoptosis. Further, it is often predicted that small changes in proliferation or apoptosis can explain the development of a structural birth defect. One flaw with this logic is that little is known about the relationships between proliferation and morphology in the face. Does proliferation actually play a role in the normal directional outgrowth and morphological changes which pattern the developing face? Here, we set out to understand the spatial distribution of proliferation in the developing mouse face and relate regional proliferation to the growth of the face over a small span of developmental time (E10‐E11). We use light sheet microscopy to capture total and proliferating nuclei in 30 E10.5 to 11.5 mouse embryo heads. Cells are quantified using a convolutional neural network methodology that has similar accuracy in cell identification to the between observer error. From these images, we then generate an atlas using linear and non‐linear transformation and perform analysis of embryo morphology and distribution of proliferation relative to total cells. Models of proliferation and its ability to alter morphology are generated in PhysiCell (http://www.physicell.org). We identify regions where there is both change in proliferation and morphology that relates to changes in the number of tail somites. We also use the spatial data gathered from these to inform a model of growth of the maxillary prominence to determine how much proliferation is likely to contribute to the directional growth of the maxilla.