Photic inhibition of TrkB/Ras activity in the pigeon's tectum during development: impact on brain asymmetry formation.

Asymmetric photic stimulation during embryonic or post-hatch development induces a functional lateralization of the pigeon's visual system, which is accompanied by left-right differences in tectal cell sizes. The intracellular membrane-anchored GTPase Ras can be activated by a number of upstream mechanisms including binding of brain-derived neurotrophic factor to its specific TrkB receptor. Ras activity plays an important morphogenetic role in neurons and therefore might also be involved in the asymmetric differentiation of tectal cells. To investigate the role of Ras, we determined the relative levels of activated Ras and of signalling active phospho-TrkB in tecta of light- and dark-incubated pigeons and combined this with an immunohistochemical detection of Ras-GTP and TrkB receptors. While Ras activation levels did not differ between light- and dark-incubated pigeons during embryonic development, directly after hatching Ras activity was significantly decreased in the stronger stimulated left tectum of light-incubated animals. This was accompanied by lower levels of TrkB phosphorylation. Immunohistochemical staining revealed Ras-GTP-positive cell bodies within the efferent cell layer. These cells were TrkB-positive and developed enlarged soma sizes within the right tectum during the first week after hatching. This association suggests asymmetric Ras activation to be involved in the asymmetric differentiation of the efferent cells as a result of asymmetric TrkB signalling. Because asymmetric light exposure occurs only during embryonic development, the observed transient asymmetric inhibition of TrkB/Ras activity after hatching may reflect differential embryonic maturation of tectal inhibitory circuits leading to a functional superiority of the right eye in the adult organism.