Drosophila E-cadherin and its binding partner Armadillo/ beta-catenin are required for axonal pathway choices in the...

The fly brain is formed by approximately hundred paired lineages of neurons, each lineage derived from one neuroblast. Embryonic neuroblasts undergo a small number of divisions and produce the primary neurons that form the functioning larval brain. In the larva, neuroblasts produce the secondary lineages that make up the bulk of the adult brain. Axons of a given secondary lineage fasciculate with each other and form a discrete bundle, the secondary axon tract (SAT). Secondary axon tracts prefigure the long axon connections of the adult brain, and therefore pathway choices of SATs made in the larva determine adult brain circuitry. Drosophila Shotgun/E-cadherin (DE-cad) and its binding partner Armadillo/beta-catenin (beta-cat) are expressed in newly born secondary neurons and their axons. The fact that the highly diverse, yet invariant pattern of secondary lineages and SATs has been recently mapped in the wild-type brain enabled us to investigate the role of DE-cad and beta-cat with the help of MARCM clones. Clones were validated by their absence of DE-cad immuno-reactivity. The most significant phenotype consists in the defasciculation and an increased amount of branching of SATs at the neuropile-cortex boundary, as well as subtle changes in the trajectory of SATs within the neuropile. In general, only a fraction of mutant clones in a given lineage showed structural abnormalities. Furthermore, although they all globally express DE-cad and beta-cat, lineages differ in their requirement for DE-cad function. Some lineages never showed morphological abnormalities in MARCM clones, whereas others reacted with abnormal branching and changes in SAT trajectory at a high frequency. We conclude that DE-cad/beta-cat form part of the mechanism that control branching and trajectory of axon tracts in the larval brain.