Twisting of the zebrafish heart tube during cardiac looping is a tbx5-dependent and tissue-intrinsic process.

Organ laterality refers to the left-right asymmetry in disposition and conformation of internal organs and is established during embryogenesis. The heart is the first organ to display visible left-right asymmetries through its left-sided positioning and rightward looping. Here, we present a new zebrafish loss-of-function allele for tbx5a, which displays defective rightward cardiac looping morphogenesis. By mapping individual cardiomyocyte behavior during cardiac looping, we establish that ventricular and atrial cardiomyocytes rearrange in distinct directions. As a consequence, the cardiac chambers twist around the atrioventricular canal resulting in torsion of the heart tube, which is compromised in tbx5a mutants. Pharmacological treatment and ex vivo culture establishes that the cardiac twisting depends on intrinsic mechanisms and is independent from cardiac growth. Furthermore, genetic experiments indicate that looping requires proper tissue patterning. We conclude that cardiac looping involves twisting of the chambers around the atrioventricular canal, which requires correct tissue patterning by Tbx5a.

Evolution of multicellularity by collective integration of spatial information.

At the origin of multicellularity, cells may have evolved aggregation in response to predation, for functional specialisation or to allow large-scale integration of environmental cues. These group-level properties emerged from the interactions between cells in a group, and determined the selection pressures experienced by these cells. We investigate the evolution of multicellularity with an evolutionary model where cells search for resources by chemotaxis in a shallow, noisy gradient. Cells can evolve their adhesion to others in a periodically changing environment, where a cell's fitness solely depends on its distance from the gradient source. We show that multicellular aggregates evolve because they perform chemotaxis more efficiently than single cells. Only when the environment changes too frequently, a unicellular state evolves which relies on cell dispersal. Both strategies prevent the invasion of the other through interference competition, creating evolutionary bi-stability. Therefore, collective behaviour can be an emergent selective driver for undifferentiated multicellularity.

All multicellular organisms, from fungi to humans, started out life as single cell organisms. These cells were able to survive on their own for billions of years before aggregating together to form multicellular groups. Although there are trade-offs for being in a group, such as sharing resources, there are also benefits: in a group, single cells can divide tasks amongst themselves to become more efficient, and can develop sophisticated mechanisms to protect each other from harm. But what compelled single cells to make the first move and aggregate into a group? One way to answer this question is to study the behaviour of slime moulds. These organisms exist as single cells but form colonies when their resources run low. Researchers have observed that slime mould colonies can navigate their environment much better than single cells alone. This property suggests that the benefits of moving together as a collective could be the driving factor propelling single cells to form groups. To test this theory, Colizzi et al. developed a computer model to examine how well groups of cells and lone individuals responded to nearby chemical cues. Unlike previous simulations, the model created by Colizzi et al. did not specify that being in a group was necessarily more favourable than existing as a single cell. Instead, it was left for evolution to decide which was the best option in response to the changing environmental conditions of the simulation. The mathematical model showed that groups of cells were generally better at sensing and moving towards a resource than single cells acting alone. Single cells moved at the same speed as groups, but they often sensed their environment poorly and got disorientated. Only when the environment changed frequently, did cells revert back to the single life. This was because it was no longer beneficial to band together as a group, as the cells were unable to sense the environmental cues fast enough to communicate to each other and coordinate a response. This work provides insights into what drove the early evolution of complex life and explains why, under certain conditions, single cells evolved to form colonies. Additionally, if this model were to be adopted by cancer biologists, it could help researchers better understand how cancer cells form groups to move and spread around the body.