nuclear receptor unfulfilled regulates axonal guidance and cell identity of drosophila mushroom body neurons核受体实现调节轴突引导和细胞的身份蘑菇体果蝇神经元.pdfVIP

Nuclear Receptor Unfulfilled Regulates Axonal Guidance and Cell Identity of Drosophila Mushroom Body Neurons 1 2 1,2 Suewei Lin , Yaling Huang , Tzumin Lee * 1 Department of Neurobiology, University of Massachusetts Medical School, Worcester, Massachusetts, United States of America, 2 Janelia Farm Research Campus, Howard Hughes Medical Institute, Ashburn, Virginia, United States of America Abstract Nuclear receptors (NRs) comprise a family of ligand-regulated transcription factors that control diverse critical biological processes including various aspects of brain development. Eighteen NR genes exist in the Drosophila genome. To explore their roles in brain development, we knocked down individual NRs through the development of the mushroom bodies (MBs) by targeted RNAi. Besides recapitulating the known MB phenotypes for three NRs, we found that unfulfilled (unf), an ortholog of human photoreceptor specific nuclear receptor (PNR), regulates axonal morphogenesis and neuronal subtype identity. The adult MBs develop through remodeling of c neurons plus de-novo elaboration of both a9/ b9 and a/ b neurons. Notably, unf is largely dispensable for the initial elaboration of c neurons, but plays an essential role in their re-extension of axons after pruning during early metamorphosis. The subsequently derived MB neuron types also require unf for extension of axons beyond the terminus of the pruned bundle. Tracing single axons revealed misrouting rather than simple truncation. Further, silencing unf in single-cell clones elicited misguidance of axons in otherwise unperturbed MBs. Such axon guidance defects may occur as MB neurons partially lose their subtype identity, as evidenced by suppression of various MB