Lola regulates Drosophila olfactory projection neuron identity and targeting specificity

We find that the loss of longitudinals lacking (lola), which encodes a BTB-Zn-finger transcription factor with 20 predicted splice isoforms, results in wiring defects in both axons and dendrites of all lineages of PNs. RNA in situ hybridization and quantitative RT-PCR suggest that most if not all lola isoforms are expressed in all PNs, but different isoforms are expressed at widely varying levels. Overexpression of individual lola isoforms fails to rescue the lola null phenotypes and causes additional phenotypes. Loss of lola also results in ectopic expression of Gal4 drivers in multiple cell types and in the loss of transcription factor gene lim1 expression in ventral PNs.Our results indicate that lola is required for wiring of axons and dendrites of most PN classes, and suggest a need for its molecular diversity. Expression pattern changes of Gal4 drivers in lola-/- clones imply that lola normally represses the expression of these regulatory elements in a subset of the cells surrounding the AL. We propose that Lola functions as a general transcription factor that regulates the expression of multiple genes ultimately controlling PN identity and wiring specificity.Nervous systems exhibit highly reproducible patterns of connectivity that are essential for their proper functions. Axon pathfinding in many systems is heavily dependent upon genetically programmed expression of guidance factors and their receptors [1]. Recent studies have indicated that dendrite target selection and aspects of synapse specificity can also be precisely genetically programmed in flies [2] and vertebrates [3]. For example, wiring specificity in the adult Drosophila olfactory system is achieved during pupal development before the onset of olfactory receptor expression [4]. Olfactory receptor neurons (ORNs) project their axons to glomeruli in the antennal lobe (AL), where they synapse with the dendrites of projection neurons (PNs) (Figure 1a; reviewed in [5,6]). PNs target their dendrites to s