TABLE 3.
Examples of Molecular-Genetic Perturbations That Influence LR Asymmetry When Not Targeted to GRP (Ciliated Organ) Precursorsa
| Construct or reagent | Blastomeres’ injection penetrance (total N examined) | Reference |
|---|---|---|
| Connexin43 gap junction mRNA | Dorsal cells → 5% heterotaxia (176) Ventral cells → 22% heterotaxia (149) |
(Levin and Mercola, 1998) |
| Connexin26 gap junction mRNA | Ventral cells → 32% heterotaxia | (Levin and Mercola, 1998) |
| Planarian (Smed) innexin11 gap junction mRNA | Dorsal cells → 12% heterotaxia (17) Ventral cells → 35% heterotaxia (72) |
(Oviedo and Levin, 2007) |
| Planarian (D.j.) innexin11 gap junction mRNA | Ventral cells → 35% heterotaxia (39) | (Oviedo and Levin, 2007) |
| SERT mutant D98G mRNA | Dorsal left cells → 7% heterotaxia Right ventral cells → 18% heterotaxia (179) |
(Fukumoto et al., 2005a) |
| LY-278,584 | Dorsal left cells → 4% heterotaxia | (Fukumoto et al., 2005b) |
| (5HT-R3 antagonist) | Right ventral cells → 18% heterotaxia | |
| Serotonin binding protein mRNA | Dorsal left cells → 7% heterotaxia Right ventral cells → 20% heterotaxia (201) |
(Fukumoto et al., 2005b) |
| Inversin protein overexpression | Right side cells → 46% (205) Left side cells → 4% (126) |
(Yasuhiko et al., 2001) |
| PKC-γ morpholinos (PCP loss-of-function) | Right ventral cells → 43% (>60) Left ventral cells → 4% (>60) |
(Kramer et al., 2002) |
One way of reconciling the proposal of nodal cilia as the initiator of asymmetry with the data set implicating ion transporters in LR patterning is a model in which ion transporters and serotonergic pathway members function on cilia or at the node. This model predicts that constructs functionally disruptive of these pathways should have the most effect when targeted to the cells that give rise to the ciliated organ. The GRP has been reverse fate-mapped (Schweickert et al., 2007; Blum et al., 2009) and is known to arise from dorsal cells; moreover, ciliary function on the right side of the node is dispensable for asymmetry (Vick et al., 2009). In contrast, a number of constructs (including the “ciliary” protein Inversin) have their maximum effect when injected on the right and/or ventral side, which according to the GRP model should have no consequence for cilia-dependent events. This proposal is also not consistent with published data on the timing of involvement of physiological events in the LR pathway (Yost, 1991; Fukumoto et al., 2005a; Fukumoto et al., 2005b; Adams et al., 2006; Danilchik et al., 2006; Vandenberg and Levin, 2010).