Expression of doublecortin correlates with neuronal migration and pattern formation in diverse regions of the developing chick brain.

The development of functional layers in the brain involves spatially and temporally regulated gene expression. Through cDNA library screening, we have identified genes that are expressed in a neural-specific manner during brain development. Sequencing and expression data indicate that one of the clones, 18C15, is the chick homologue of doublecortin, a human X-linked gene found to be mutated in subcortical laminar heterotopia (double cortex syndrome) and lissencephaly. The 18C15 mRNA contains multiple motifs that are known to regulate mRNA stability in response to inductive signals, and these motifs are conserved between the chick and human sequences. Doublecortin is found to be expressed at peak levels during early development of the cerebellum and forebrain, and is expressed in other regions including the tectum, spinal cord, and dorsal root ganglia. This study demonstrates both spatial and temporal regulation of doublecortin expression in the chick, which is associated with early events in brain development, including neuronal migration.

Thy-1 and AvGp50 signal transduction complex in the avian nervous system: c-Fyn and G alpha i protein association and activation of signalling pathways.

We have previously reported the isolation of two distinct populations of detergent resistant membrane complexes (DRMC's) from day-old chick brain (Henke et al.: J Neurosci Res 45:617-630, 1996). We now show that the glycosylphosphatidylinositol-anchored proteins Thy-1 and AvGp50 are associated in a signalling complex with c-Fyn, the heterotrimeric G alpha i subfamily members G alpha i-3, G alpha z, and G alpha o, alpha and beta tubulin, and a number of other phosphoproteins in immunocomplexes isolated from both populations of DRMC's. Activation of this signalling complex via Thy-1 monoclonal antibody incubation with chick forebrain cells, elicited a decrease in total phosphoprotein profile and tyrosine kinase activity present in DRMC fractions isolated from these cells, while AvGp50 and control antibodies had no effect. Down-regulation of the DRMC phosphoprotein profile was accompanied by an increase in the Thy-1-associated signalling complex, suggesting that activation of this complex initiates the decreases seen in overall DRMC kinase activity. This signalling complex provides the basis for GPI-anchored protein-mediated signal transduction within the unique plasma membrane domains represented by DRMC's.