@article {6454, title = {Extremes of lineage plasticity in the Drosophila brain.}, journal = {Current Biology}, volume = {23}, year = {2013}, month = {2013 Sep 19}, pages = {1908-13}, abstract = {

An often-overlooked aspect of neural plasticity is the plasticity of neuronal composition, in which the numbers of neurons of particular classes are altered in response to environment and experience. The Drosophila brain features several well-characterized lineages in which a single neuroblast gives rise to multiple neuronal classes in a stereotyped sequence during development [1]. We find that in the\ intrinsic mushroom body neuron lineage, the numbers for each class are highly plastic, depending on the timing of temporal fate transitions and the rate of neuroblast proliferation. For example, mushroom body neuroblast cycling can continue under starvation conditions, uncoupled from\ temporal fate transitions that depend on extrinsic cues reflecting organismal growth and development. In contrast, the proliferation rates of antennal lobe lineages are closely associated with organismal development, and\ their temporal fate changes appear to be cell cycle-dependent, such that the same numbers and types of uniglomerular projection neurons innervate the antennal lobe following various perturbations. We propose that this surprising difference in plasticity for these brain lineages is adaptive, given their respective roles as parallel\ processors versus discrete carriers of olfactory information.

}, issn = {1879-0445}, doi = {10.1016/j.cub.2013.07.074}, author = {Lin, Suewei and Marin, Elizabeth C and Yang, Ching-Po and Kao, Chih-Fei and Apenteng, Bettye A and Huang, Yaling and O{\textquoteright}Connor, Michael B and Truman, James W and Lee, Tzumin} } @article {4488, title = {Generating neuronal diversity in the Drosophila central nervous system.}, journal = {Developmental Dynamics: An Official Publication of the American Association of Anatomists}, volume = {241}, year = {2012}, month = {2012 Jan}, pages = {57-68}, abstract = {

Generating diverse neurons in the central nervous system involves three major steps. First, heterogeneous neural progenitors are specified by positional cues at early embryonic stages. Second, neural progenitors sequentially produce neurons or intermediate precursors that acquire different temporal identities based on their birth-order. Third, sister neurons produced during asymmetrical terminal mitoses are given distinct fates. Determining the molecular mechanisms underlying each of these three steps of cellular diversification will unravel brain development and evolution. Drosophila has a relatively simple and tractable CNS, and previous studies on Drosophila CNS development have greatly advanced our understanding of neuron fate specification. Here we review those studies and discuss how the lessons we have learned from fly teach us the process of neuronal diversification in general.

}, issn = {1097-0177}, doi = {10.1002/dvdy.22739}, author = {Lin, Suewei and Lee, Tzumin} } @article {6290, title = {Lineage analysis of Drosophila lateral antennal lobe neurons reveals notch-dependent binary temporal fate decisions.}, journal = {PLoS Biology}, volume = {10}, year = {2012}, month = {2012 Nov 20}, pages = {e1001425}, abstract = {

Binary cell fate decisions allow the production of distinct sister neurons from an intermediate precursor. Neurons are further diversified based on the birth order of intermediate precursors. Here we examined the interplay between binary cell fate and birth-order-dependent temporal fate in the Drosophila lateral antennal lobe (lAL) neuronal lineage. Single-cell mapping of the lAL lineage by twin-spot mosaic analysis with repressible cell markers (ts-MARCM) revealed that projection neurons (PNs) and local interneurons (LNs) are made in pairs through binary fate decisions. Forty-five types of PNs innervating distinct brain regions arise in a stereotyped sequence; however, the PNs with similar morphologies are not necessarily born in a contiguous window. The LNs are morphologically less diverse than the PNs, and the sequential morphogenetic changes in the two pairs occur independently. Sanpodo-dependent Notch activity promotes and patterns the LN fates. By contrast, Notch diversifies PN temporal fates in a Sanpodo-dispensable manner. These pleiotropic Notch actions underlie the differential temporal fate specification of twin neurons produced by common precursors within a lineage, possibly by modulating postmitotic neurons{\textquoteright} responses to Notch-independent transcriptional cascades.

}, keywords = {Animals, Biological Markers, Brain, Cell Division, Cell Lineage, Cellular, Developmental, Drosophila, Drosophila Proteins, Embryo, Gene Expression Regulation, Genes, Immunohistochemistry, Insect, Larva, Mechanotransduction, Nerve Tissue Proteins, Neurogenesis, Neurons, Nonmammalian, Notch, Receptors, Single-Cell Analysis}, issn = {1545-7885}, doi = {10.1371/journal.pbio.1001425}, author = {Lin, Suewei and Kao, Chih-Fei and Yu, Hung-Hsiang and Huang, Yaling and Lee, Tzumin} } @article {782, title = {Lineage-specific effects of Notch/Numb signaling in post-embryonic development of the Drosophila brain.}, journal = {Development}, volume = {137}, year = {2010}, month = {2010 Jan}, pages = {43-51}, abstract = {

Numb can antagonize Notch signaling to diversify the fates of sister cells. We report here that paired sister cells acquire different fates in all three Drosophila neuronal lineages that make diverse types of antennal lobe projection neurons (PNs). Only one in each pair of postmitotic neurons survives into the adult stage in both anterodorsal (ad) and ventral (v) PN lineages. Notably, Notch signaling specifies the PN fate in the vPN lineage but promotes programmed cell death in the missing siblings in the adPN lineage. In addition, Notch/Numb-mediated binary sibling fates underlie the production of PNs and local interneurons from common precursors in the lAL lineage. Furthermore, Numb is needed in the lateral but not adPN or vPN lineages to prevent the appearance of ectopic neuroblasts and to ensure proper self-renewal of neural progenitors. These lineage-specific outputs of Notch/Numb signaling show that a universal mechanism of binary fate decision can be utilized to govern diverse neural sibling differentiations.

}, keywords = {Animals, Apoptosis, Biological, Brain, Developmental, Drosophila, Drosophila Proteins, Gene Expression Regulation, Immunohistochemistry, Juvenile Hormones, Models, Nerve Tissue Proteins, Neurons, Notch, POU Domain Factors, Receptors, Signal Transduction}, issn = {1477-9129}, doi = {10.1242/dev.041699}, author = {Lin, Suewei and Lai, Sen-Lin and Yu, Huang-Hsiang and Chihara, Takahiro and Luo, Liqun and Lee, Tzumin} } @article {4274, title = {Nuclear receptor unfulfilled regulates axonal guidance and cell identity of Drosophila mushroom body neurons.}, journal = {PLoS One}, volume = {4}, year = {2009}, month = {2009 Dec 22}, pages = {e8392}, 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 gamma neurons plus de-novo elaboration of both alpha{\textquoteright}/beta{\textquoteright} 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.

}, keywords = {Aging, Animals, Axons, Biological Markers, Cytoplasmic and Nuclear, Drosophila melanogaster, Drosophila Proteins, Gene Knockdown Techniques, Gene Silencing, MicroRNAs, Morphogenesis, Mushroom Bodies, Phenotype, Receptors}, issn = {1932-6203}, doi = {10.1371/journal.pone.0008392}, author = {Lin, Suewei and Huang, Yaling and Lee, Tzumin} } @article {792, title = {Gradients of the Drosophila Chinmo BTB-zinc finger protein govern neuronal temporal identity.}, journal = {Cell}, volume = {127}, year = {2006}, month = {2006 Oct 20}, pages = {409-22}, abstract = {

Many neural progenitors, including Drosophila mushroom body (MB) and projection neuron (PN) neuroblasts, sequentially give rise to different subtypes of neurons throughout development. We identified a novel BTB-zinc finger protein, named Chinmo (Chronologically inappropriate morphogenesis), that governs neuronal temporal identity during postembryonic development of the Drosophila brain. In both MB and PN lineages, loss of Chinmo autonomously causes early-born neurons to adopt the fates of late-born neurons from the same lineages. Interestingly, primarily due to a posttranscriptional control, MB neurons born at early developmental stages contain more abundant Chinmo than their later-born siblings. Further, the temporal identity of MB progeny can be transformed toward earlier or later fates by reducing or increasing Chinmo levels, respectively. Taken together, we suggest that a temporal gradient of Chinmo (Chinmo(high) {\textendash}\> Chinmo(low)) helps specify distinct birth order-dependent cell fates in an extended neuronal lineage.

}, keywords = {5{\textquoteright} Untranslated Regions, Amino Acid Sequence, Animals, Brain, Cell Differentiation, Cell Lineage, Developmental, Drosophila, Drosophila Proteins, Gene Expression Regulation, Larva, Molecular Sequence Data, Morphogenesis, Mushroom Bodies, Mutation, Nerve Tissue Proteins, Neurons, Post-Translational, Protein Processing, Time Factors, Transgenes, Zinc Fingers}, issn = {0092-8674}, doi = {10.1016/j.cell.2006.08.045}, author = {Zhu, Sijun and Lin, Suewei and Kao, Chih-Fei and Awasaki, Takeshi and Chiang, Ann-Shyn and Lee, Tzumin} }