The G12 subfamily of heterotrimeric G-proteins consists of two members, G 12 and G13. Gene-targeting studies have revealed a role for G 13 in blood vessel development. Mice lacking the ␣ subunit of G 13 die around embryonic day 10 as the result of an angiogenic defect. On the other hand, the physiological role of G12 is still unclear. To address this issue, we generated G␣ 12-deficient mice. In contrast to the G␣ 13-deficient mice, G␣12-deficient mice are viable, fertile, and do not show apparent abnormalities. However, G␣ 12 does not seem to be entirely redundant, because in the offspring generated from G␣ 12؎ G␣13؎ intercrosses, at least one intact G␣12 allele is required for the survival of animals with only one G␣13 allele. In addition, G␣12 and G␣13 showed a difference in mediating cell migratory response to lysophosphatidic acid in embryonic fibroblast cells. Furthermore, mice lacking both G␣ 12 and G␣q die in utero at about embryonic day 13. These data indicate that the G␣ 12-mediated signaling pathway functionally interacts not only with the G␣ 13-but also with the G␣q/11-mediated signaling systems.

Information processing in the vertebrate brain is thought to be mediated through distributed neural networks, but it is still unclear how sensory stimuli are encoded and detected by these networks, and what role synaptic inhibition plays in this process. Here we used a collision avoidance behavior in Xenopus tadpoles as a model for stimulus discrimination and recognition. We showed that the visual system of the tadpole is selective for behaviorally relevant looming stimuli, and that the detection of these stimuli first occurs in the optic tectum. By comparing visually guided behavior, optic nerve recordings, excitatory and inhibitory synaptic currents, and the spike output of tectal neurons, we showed that collision detection in the tadpole relies on the emergent properties of distributed recurrent networks within the tectum. We found that synaptic inhibition was temporally correlated with excitation, and did not actively sculpt stimulus selectivity, but rather it regulated the amount of integration between direct inputs from the retina and recurrent inputs from the tectum. Both pharmacological suppression and enhancement of synaptic inhibition disrupted emergent selectivity for looming stimuli. Taken together these findings suggested that, by regulating the amount of network activity, inhibition plays a critical role in maintaining selective sensitivity to behaviorally-relevant visual stimuli.

Heterotrimeric G proteins are critical cellular signal transducers. They are known to directly relay signals from seven-transmembrane G protein-coupled receptors (GPCRs) to downstream effectors. On the other hand, receptor tyrosine kinases (RTKs), a different family of membrane receptors, signal through docking sites in their carboxy-terminal tails created by autophosphorylated tyrosine residues. Here we show that a heterotrimeric G protein, G alpha(13), is essential for RTK-induced migration of mouse fibroblast and endothelial cells. G alpha(13) activity in cell migration is retained in a C-terminal mutant that is defective in GPCR coupling, suggesting that the migration function is independent of GPCR signaling. Thus, G alpha(13) appears to be a critical signal transducer for RTKs as well as GPCRs. This broader role of G alpha(13) in cell migration initiated by two types of receptors could provide a molecular basis for the vascular system defects exhibited by G alpha(13) knockout mice.