Thrilled to see our latest work online @Dev_Cell! 🥳 How do cells build functional organs with precision?🫀🫁📏 Here, we show how coupling of cell shape and organ function tunes the form and contractile power of the developing #zebrafish heart 1/n https://t.co/lBXokFmsPx

How the functional architecture of the zebrafish heart is shaped during development 📹@tobyandrews et al @_Priya_R lab @TheCrick in @Dev_Cell ➡️ https://t.co/RpF2fe16XM

@jake_cs_ @Kirti_Guptatifr @briscoejames @TheCrick Heartiest congratulations and thanks to @_Priya_R on the first of many studies from the lab, and for supporting me through its morphogenesis from start to finish🫀

@jake_cs_ A huge thanks to all authors for their work in bringing this project to life @jake_cs_ @Kirti_Guptatifr @briscoejames and our colleagues and facilities @TheCrick 13/n

@jake_cs_ 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

@jake_cs_ 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

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

@jake_cs_ 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 @jake_cs_ 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

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

Morphogens in the evolution of size, shape and patterning In this Review, Lewis Mosby, Amy Bowen and @z_hvas @TheCrick @UCL explore how morphogen-mediated patterning evolve and how theory and experiment can be interwoven to bring new perspectives: https://t.co/hDA4S509JJ

Fantastic imaging! Check out Toby's preprint on heart mechanobiology.

It was a lot of fun collaborating with @tobyandrews @_Priya_R on modelling mechanisms of organ-scale stretch. Check out Toby’s 🧵👇

@jake_cs_ @mc_mcramel @Kirti_Guptatifr @briscoejames @_Priya_R @CALM_STP And get in touch with any questions, we'd love to hear what you think!