Visceral organ morphogenesis via calcium-patterned muscle contractions

How organs achieve their final shape is a problem at the interface between physics and developmental biology. Organs often involve multiple interacting tissue layers that must be coordinated to orchestrate the complex shape changes of development. Intense study uncovered genetic, and physical ingredients driving the form of mono layer tissue. Yet, tracing dynamics across tissue layers, and scales - from cell to tissue, to entire organs - remains an outstanding challenge. Here, we study the midgut of Drosophila embryos as a model visceral organ, to reconstruct in toto the dynamics of multi-layer organ formation in vivo. Using light-sheet microscopy, genetics, computer vision, and tissue cartography, we extract individual tissue layers to map the time course of shape across scales from cells to organ. We identify the kinematic mechanism driving the shape change due to tissue layer interactions by linking out-of-plane motion to active contraction patterns, revealing a convergent extension process in which cells deform as they flow into deepening folds. Acute perturbations of contractility in the muscle layer using non-neuronal optogenetics reveals that these contraction patterns are due to muscle activity, which induces cell shape changes in the adjacent endoderm layer. This induction cascade relies on high frequency calcium pulses in the muscle layer, under the control of hox genes. Inhibition of targets of calcium involved in myosin phosphorylation abolishes constrictions. Our study of multi-layer organogenesis reveals how genetic patterning in one layer triggers a dynamic molecular mechanism to control a physical process in the adjacent layer, to orchestrate whole-organ shape change.