TABLE 2.
Specific Predictions and the Fit of the Three Main Models to These Dataa
Experimental question | Cilia model predicts | Cytoplasmic model predicts | Chromatid segregation model predicts | Experimental result |
---|---|---|---|---|
Should mutation of kinesin, dynein, MTOC, and PCP proteins randomize LR? | YES | YES | YES | YES |
Should viscosity changes at the node randomize LR? | YES | no, unless cilia amplify | no, unless cilia amplify | YES |
Should chick embryos have asymmetric gene expression before node forms? | NO | YES | YES | YES |
Should frog embryos establish asymmetric gradients long before cilia form? | NO | YES | YES | YES |
Should disruption of cytoskeleton or of physiological asymmetries only during the first couple of cleavages randomize LR? | NO | YES | YES | YES |
Should chick node receive LR information from lateral tissue? | NO | YES | NO | YES |
Should embryos (human & newt) randomize if split at the two-cell stage? | NO | YES | YES | YESb |
Should the brains of primary ciliary dyskinesia patients have normal laterality? | NO | YES | YES | YES |
Should any mutants exist with abnormal ciliary flow but normal LR asymmetry? | NO | YES | YES | YES |
Should animals and plants with no cilia and no node be able to establish asymmetry using some of the same molecules as ciliated vertebrates? | NO | YES | YES | YES |
Should organizers induced past the first few cleavages be randomized? | NO | YES | YES | YES |
The three main models make distinct predictions as to the outcomes of a number of experimental questions. Most work on cilia has focused on mutations of ciliary genes, which does not distinguish between these models (since many of these same components also play important roles in intracellular polarity determination and are present in non-ciliated cells). However, a variety of extant data do distinguish between the models; with the exception of the two studies that have shown that fluid flow per se can affect asymmetry (clearly supporting the ciliary model), the majority of the data support the early models, not the ciliary model. Green = consistent and predicted by model. Yellow = not predicted by model but does not contradict it. Red = contradicts the predictions of the model; LR, left–right.
Human twins show subtle bookending (opposite asymmetry of unilateral defects), not real laterality disturbances.