Heartiest congratulations and thanks to @rashmi-priya.bsky.social on the first of many studies from the lab, and for supporting me through its morphogenesis from start to finish 🫀

A huge thanks to all authors for their work in bringing this project to life @jcornwallscoones.bsky.social @mcramel.bsky.social @kirtigupta.bsky.social @jamesbriscoe.bsky.social and our colleagues and facilities @crick.ac.uk 13/n

Looking forward - a deeper understanding of these design principles will give us better insight into what makes development robust, and how it can be steered to produce diversity, novelty, and disease 12/n

Together, we learn that the shape and size of the heart aren’t hardwired, instead they’re worked out through a flow of information across scales, giving rise to self-organising and emergent features 👀 11/n

Not only this, they were also more functionally efficient, owing to a greater blood filling capacity. 10/n

To test the model, we came up with a neat genetic approach to disrupt actin turnover in the Notch+ population. Following the model predictions, when activated at sufficient density, this made hearts bigger... 9/n

To understand how coherent changes in organ shape and size could arise from stochastic signalling @jcornwallscoones.bsky.social developed a 3D vertex model, which predicted the ventricle should grow suddenly, when enough cells soften 8/n

Looking more closely, we found intrinsic changes in actomyosin tension enable stretched cells to change shape in response to organ scale forces. This is a local response to Notch, activated in a stochastic pattern 7/n

Using drugs to disrupt the heartbeat, we found cells stretch in response to the force of ventricle contraction. This also traps them in the compact layer, meaning trabecular density stabilises at a threshold of force production 6/n

meanwhile, by unwrapping the heart, we found that compact layer cells stretch. This allows the heart to grow in size despite losing cells from its outer layer 5/n

Using single cell tracking, we found trabecular cells don’t just divide to form ridges. Instead, they recruit cells from the surrounding compact layer... 4/n

As the embryo grows, the heart expands in size and forms two layers – an elastic compact layer, and an inner layer of muscular trabecular ridges that help to power heart contraction 3/n

The heart is a remarkable organ, where form and function arise in parallel – in this case, the heart wall remodels to form a complex architecture, while the heart beats to support blood flow to the peripheral organs 2/n

Spheroids are simple systems with only convex curvature. What about more complex systems?

We teamed up with @tobyandrews.bsky.social & @rashmi-priya.bsky.social, and analyzed the ventricular myocardium of Zebrafish hearts ... and it works! 👇

(Directors: high alignment = red, misaligned = blue)