Morphology of Embryonic Epidermis: An Empirical Multiscale Biophysics Approach*

Between nanoscale genotype and mesoscale phenotype, a cascade of physical and biological events take place that translate coded DNA into biological shape, function, and form. But how does this happen? How do we coarse grain from –omics regulation to quasi-pre-programmed anatomical patterns? Here, we use embryonic mouse epidermis as a specific test case to address these questions. Empirical measurements are acquired using the Molecular Atlas Platform – a multiscale imaging technology for visualizing proteomic data across many orders of magnitude in scale – and DNA-PAINT for highly multiplexed super-resolution imaging of immunofluorescent stained molecular targets. We focus on studying the biomechanics of pattern formation, and the sequence of events leading to stem cell fate specification. Our results lead us to a head-on collision with a fundamental chick-and-egg question: Does genetic programming pattern morphology, or do the material effects of morphology pattern gene expression?