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3 Janelia Publications

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    12/22/09 | Nuclear receptor unfulfilled regulates axonal guidance and cell identity of Drosophila mushroom body neurons.
    Lin S, Huang Y, Lee T
    PLoS One. 2009 Dec 22;4(12):e8392. doi: 10.1371/journal.pone.0008392

    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 gamma neurons plus de-novo elaboration of both alpha’/beta’ and alpha/beta neurons. Notably, unf is largely dispensable for the initial elaboration of gamma 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 subtype markers in unf knockdown MBs. In sum, unf governs axonal morphogenesis of multiple MB neuron types, possibly through regulating neuronal subtype identity.

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    08/01/09 | New genetic tools for cell lineage analysis in Drosophila.
    Lee T
    Nature Methods. 2009 Aug;6(8):566-8. doi: 10.1038/nmeth0809-566

    Real-time lineage tracing in flies gets a boost with three techniques to specifically label a progenitor’s daughter cells.

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    07/01/09 | Twin-spot MARCM to reveal the developmental origin and identity of neurons.
    Yu H, Chen C, Shi L, Huang Y, Lee T
    Nature Neuroscience. 2009 Jul;12(7):947-53. doi: 10.1038/nn.2345

    A comprehensive understanding of the brain requires the analysis of individual neurons. We used twin-spot mosaic analysis with repressible cell markers (twin-spot MARCM) to trace cell lineages at high resolution by independently labeling paired sister clones. We determined patterns of neurogenesis and the influences of lineage on neuron-type specification. Notably, neural progenitors were able to yield intermediate precursors that create one, two or more neurons. Furthermore, neurons acquired stereotyped projections according to their temporal position in various brain sublineages. Twin-spot MARCM also permitted birth dating of mutant clones, enabling us to detect a single temporal fate that required chinmo in a sublineage of six Drosophila central complex neurons. In sum, twin-spot MARCM can reveal the developmental origins of neurons and the mechanisms that underlie cell fate.

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