TABLE 1.

Fundamental Features of Three Main Models of LR Symmetry Determination^a

Feature	Predictions
	Ciliary model	Cytoplasmic model	Chromatid segregation model
Origin of asymmetry	Centriole	Centriole	Mitotic apparatus
Timing for initiation step	Gastrulation (late)	Cleavage (early)	Cleavage (early)
Amplification by	Cilia-driven fluid flow in node during gastrulation	Intracellular localization of bioelectric machinery at cleavage stages	PCP-aligned differential chromatid segregation
Evolutionary conservation	Mouse is typical vertebrate; other examples that don’t use cilia are outliers	Mouse may be an outlier; asymmetry is fundamentally very widely conserved	Mouse may be an outlier; asymmetry is fundamentally very widely conserved

^aAll three models agree on an intracellular fundamental origin of asymmetry. Although the cilia model focuses on ciliary motion, the biochemical structure of cilia (and thus their unique chirality) derives from the centriole—the same microtubule organizing center that is proposed to orient asymmetric intracellular transport in the cytoplasmic model. The chromatid segregation and cytoplasmic models propose that fundamental steps of left–right (LR) patterning occur very early, during cleavage stages, and propose planar cell polarity (PCP) or physiological systems for amplifying asymmetry on the single-cell level onto multicellular cell fields. The ciliary model proposes fluid flow in the node during gastrulation—a fundamentally multicellular process—to be the origin of consistent asymmetry. The cilia model proposes nodal flow to be a fundamental feature of vertebrate laterality, holding the mouse embryo as a prototypical model for this process, and suggests that vertebrates that pattern the LR axis prior to (or without) cilia are evolutionary outliers. In contrast, the early models suggest that the rodent embryo may instead be atypical, with chirality being a fundamental, ancient, well-conserved property of individual cells.