Left-right development: mammalian phenotypes and conceptual models

Abstract

Consistent left-right asymmetry in a population requires a special kind of developmental specification. Models of this process must account for the complex phenotypes seen when left-right is abnormal. In some human and mouse mutations, there appears to be a randomisation of global situs to either solitus or inversus, whereas in the inv/inv mouse essentially all are inversus. However, in these and all additional examples there are frequently other anomalies, including symmetry (isomerism) and discordance between organs (heterotaxia). Current models invoke a molecular chiral referent as the source of the primary handed information. We describe a new two-gradient model which accommodates all defects of situs whilst leaving the primary asymmetry unaltered.