Left-right asymmetry

Bateson (1894), in Materials for the Study of Variation, noted that the right side of a bilateral animal is an image of the left. He also noted that many substantially symmetrical forms still show asymmetry in some paired organs.¹ Child (1924), in Physiological Foundations of Behavior, discussed partial duplications in vertebrates, where visceral asymmetry is often reversed in one component.² He argued that situs inversus and mirror imaging show the components affect each other or share a common factor. He said there was as yet no experimental evidence to analyse this. Thompson, in On Growth and Form, quoted Japp that only asymmetry can beget asymmetry, and accepted this as true for chemist and biologist.³

Carneiro and colleagues (2011) described the ways laterality can fail. These are loss of asymmetry (isomerism), complete inversion (situs inversus) and random placement of single organs (heterotaxia).⁴ In Xenopus, they wrote, maternal serotonin moving through gap-junctional paths at cleavage stages dictates asymmetry upstream of the Nodal-related gene Nr1.⁵ They stated that the mechanisms linking these earlier biophysical asymmetries to transcriptional control were not known. After the first divisions, he reported, cells on the right are more negatively charged because of polarized ion gradients.⁷

Pai and colleagues (2012) observed that most studies use cardiac and visceral situs as the readout. They suggested that left-right identity may be far more widespread in the body than is appreciated. They therefore searched for asymmetries in functional physiology, citing bioelectrical determinants of patterning. The work was done in Xenopus embryos.⁶ They also pointed to a disconnect between the sidedness of organs and of the brain. Human situs inversus patients show normal right handedness and language lateralization, though some other behavioural traits are reversed.⁶

Davison and colleagues (2016) studied the pond snail, whose shell chirality is under a single maternal locus. They reported that a disabling mutation in one copy of a duplicated formin gene is perfectly associated with symmetry breaking.⁸ Contrary to existing models, they found asymmetric gene expression at the 2- and 4-cell stages, before morphological asymmetry.⁸ McMillen and Levin (2024) reviewed the vertebrate left-right axis. Many treatments randomize outcomes, but any given embryo keeps a consistent identity on each side, and all its cells agree.⁹ They knew of only one study that breaks this concordance.⁹