Genetic-Morphological Synergy Governs Cell Fate Specification in Development

Abstract

Cell morphology reflects cellular states, particularly cell fates with specific spatiotemporal features, like the spreading of epidermal cells in skin. However, how cell morphology relates to cell fate and genetic programs remains unclear. In this study, we leveraged the up-to-date lineage-resolved 3D cell morphology dataset of worm Caenorhabditis elegans embryogenesis. Twelve quantitative morphology descriptors reveal that cell morphology variation is tightly controlled and robust against mechanical compression, but not Notch signaling blocking. Integrating expression profiles of 412 genes, genetic and morphological differentiations between sister sublineages are identified in either coupled or decoupled manners, specifying cell fates from the formation of germ layers and tissues/organs to body axis establishment. Remarkably, customized morphology descriptors significantly distinguish cell fates (e.g., neuron, pharynx, muscle, intestine, skin) with a few dozen 3D cell region samples. Together, these results uncover the genetic-morphological regulatory architectures during development synergistically and point toward medical and engineering applications with cell morphologies as novel biosensors.