The fly optic lobe is composed of four ganglia; lamina, medulla, lobula, and lobula plate. Neurons in these ganglia derive from two distinct progenitor pools, the outer proliferation center (OPC) and inner proliferation center (IPC). OPC produces lamina and medulla neurons, whereas IPC generates lobula and lobula plate neurons. These neurons in each ganglion are located at specific regions to form compartments, and are never intermingled with each other at the interfaces between ganglia. However, mechanisms that inhibit cell-mixing at the borders between each ganglion have been unclear. Previously we and other group showed that cell-cell interaction through Slit-Robo signaling, an axon guidance signaling, is involved in the inhibition of cell mixing between lamina and IPC (Tayler et al., 2004) and that between medulla and IPC during larval development (Suzuki et al., in press). Since cell-mixing occurs only partially in sli or its receptors mutant larvae, additional signalings may also participate in the border formation.
Here, we show that Netrin signaling, another axon guidance signaling, regulates the border formation between medulla and IPC. The NetA and NetB ligands are expressed in IPC while their receptors Fra and Unc5 are expressed in lamina glial cells. In NetAB or fra mutants, IPC cells intruded into the medulla cortex. unc5 RNAi also caused similar phenotype. Since Fra and Unc5 are expressed in the lamina glial cells, we examined glia specific loss-of-function of Fra and Unc5, which also caused cell mixing, suggesting that glial cells play essential roles in the border formation between medulla and lobula through Netrin signaling.