The unfulfilled gene is required for the development of mushroom body neuropil in Drosophila

<p>Abstract</p> <p>Background</p> <p>The mushroom bodies (MBs) of <it>Drosophila </it>are required for complex behaviors and consist of three types of neurons, γ, α'/β' and α/β. Previously, roles for transcription factors in MB neuronal differentiation have only been described for a subset of MB neurons. We are investigating the roles of <it>unfulfilled </it>(<it>unf</it>; <it>HR51</it>, CG16801) in MB development. <it>unf </it>encodes a nuclear receptor that is orthologous to the nuclear receptors fasciculation of axons defective 1 (FAX-1) of the nematode and photoreceptor specific nuclear receptor (PNR) of mammals. Based on our previous observations that <it>unf </it>transcripts accumulate in MB neurons at all developmental stages and the presence of axon pathfinding defects in <it>fax-1 </it>mutants, we hypothesized that <it>unf </it>regulates MB axon growth and pathfinding.</p> <p>Results</p> <p>We show that <it>unf </it>mutants exhibit a range of highly penetrant axon stalling phenotypes affecting all neurons of the larval and adult MBs. Phenotypic analysis of <it>unf</it>^{<it>X1 </it>}mutants revealed that α'/β' and α/β neurons initially project axons but stall prior to the formation of medial or dorsal MB lobes. <it>unf</it>^{<it>Z0001 </it>}mutants form medial lobes, although these axons fail to branch, which results in a failure to form the α or α' dorsal lobes. In either mutant background, γ neurons fail to develop larval-specific dorsal projections. These mutant γ neurons undergo normal pruning, but fail to re-extend axons medially during pupal development. <it>unf</it>^{<it>RNAi </it>}animals displayed phenotypes similar to those seen in <it>unf</it>^{<it>Z0001 </it>}mutants. Unique asymmetrical phenotypes were observed in <it>unf</it>^<it>X1</it>/<it>unf</it>^{<it>Z0001 </it>}compound heterozygotes. Expression of <it>UAS-unf </it>transgenes in MB neurons rescues the larval and adult <it>unf </it>mutant phenotypes.</p> <p>Conclusions</p> <p>These data support the hypothesis that <it>unf </it>plays a common role in the development of all types of MB neurons. Our data indicate that <it>unf </it>is necessary for MB axon extension and branching and that the formation of dorsal collaterals is more sensitive to the loss of <it>unf </it>function than medial projections. The asymmetrical phenotypes observed in compound heterozygotes support the hypothesis that the earliest MB axons may serve as pioneers for the later-born MB neurons, providing evidence for pioneer MB axon guidance in post-embryonic development.</p