Requirement for engrailed and invected genes reveals novel regulatory interactions between engrailed/invected, patched, gooseberry and wingless during Drosophila neurogenesis

During neurogenesis, the transmembrane protein Patched (Ptc) promotes a wingless (wg)-mediated specification of a neuronal precursor cell, NB4-2, by repressing gooseberry (gsb). In this study, novel interactions of these genes with engrailed (en) and invected (inv) during neurogenesis have been uncovered. While in row 4 cells Ptc represses gsb and wg, in row 5 cells en/inv relieve Ptc repression of gsb by a non-autonomous mechanism that does not involve hedgehog (hh). This differential regulation of gsb leads to the specification of NB5-3 and NB4-2 identities to two distinct neuroblasts. The uncoupling of the ptc-gsb regulatory circuit also enables gsb to promote Wg expression in row 5 cells. Our results suggest that the en/inv → ptc → gsb → wg pathway uncovered here and the hh → wg are distinct pathways that function to maintain wild-type level of Wg. Our results also indicate that Hh is not the only ligand for Ptc and similarly Ptc is not the only receptor for Hh.