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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.

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.

Molecules that replicate in trans are vulnerable to evolutionary extinction because they decrease the catalysis of replication to become more available as a template for replication. This problem can be alleviated with higher-level selection that clusters molecules of the same phenotype, favouring those groups that contain more catalysis. Here, we study a simple replicator model with implicit higher-level selection through space. We ask whether the functionality of such system can be enhanced when molecules reproduce through complementary replication, representing RNA-like replicators. For high diffusion, symmetry breaking between complementary strands occurs: one strand becomes a specialised catalyst and the other a specialised template. In ensemble, such replicators can modulate their catalytic activity depending on their environment, thereby mitigating the conflict between levels of selection. In addition, these replicators are more evolvable, facilitating survival in extreme conditions (i.e., for higher diffusion rates). Our model highlights that evolution with implicit higher-level selection—i.e., as a result of local interactions and spatial patterning—is very flexible. For different diffusion rates, different solutions to the selective conflict arise. Our results support an RNA World by showing that complementary replicators may have various ways to evolve more complexity.