@article {6898, title = {Making Drosophila lineage-restricted drivers via patterned recombination in neuroblasts.}, journal = {Nature Neuroscience}, volume = {17}, year = {2014}, month = {2014 Apr}, pages = {631-7}, abstract = {

The Drosophila cerebrum originates from about 100 neuroblasts per hemisphere, with each neuroblast producing a characteristic set of neurons. Neurons from a neuroblast are often so diverse that many neuron types remain unexplored. We developed new genetic tools that target neuroblasts and their diverse descendants, increasing our ability to study fly brain structure and development. Common enhancer-based drivers label neurons on the basis of terminal identities rather than origins, which provides limited labeling in the heterogeneous neuronal lineages. We successfully converted conventional drivers that are temporarily expressed in neuroblasts, into drivers expressed in all subsequent neuroblast progeny. One technique involves immortalizing GAL4 expression in neuroblasts and their descendants. Another depends on loss of the GAL4 repressor, GAL80, from neuroblasts during early neurogenesis. Furthermore, we expanded the diversity of MARCM-based reagents and established another site-specific mitotic recombination system. Our transgenic tools can be combined to map individual neurons in specific lineages of various genotypes.

}, issn = {1546-1726}, doi = {10.1038/nn.3654}, author = {Awasaki, Takeshi and Kao, Chih-Fei and Lee, Ying-Jou and Yang, Ching-Po and Huang, Yaling and Pfeiffer, Barret D and Luan, Haojiang and Jing, Xiaotang and Huang, Yu-Fen and He, Yisheng and Schroeder, Mark David and Kuzin, Alexander and Brody, Thomas and Zugates, Christopher T and Odenwald, Ward F and Lee, Tzumin} } @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 {4590, title = {Hierarchical deployment of factors regulating temporal fate in a diverse neuronal lineage of the Drosophila central brain.}, journal = {Neuron}, volume = {73}, year = {2012}, month = {2012 Feb 23}, pages = {677-84}, abstract = {

The anterodorsal projection neuron lineage of Drosophila melanogaster produces 40 neuronal types in a stereotypic order. Here we take advantage of this complete lineage sequence to examine the role of known temporal fating factors, including Chinmo and the Hb/Kr/Pdm/Cas transcriptional cascade, within this diverse central brain lineage. Kr mutation affects the temporal fate of the neuroblast (NB) itself, causing a single fate to be skipped, whereas Chinmo null only elicits fate transformation of NB progeny without altering cell counts. Notably, Chinmo operates in two separate windows to prevent fate transformation (into the subsequent Chinmo-indenpendent fate) within each window. By contrast, Hb/Pdm/Cas play no detectable role, indicating that Kr either acts outside of the cascade identified in the ventral nerve cord or that redundancy exists at the level of fating factors. Therefore, hierarchical fating mechanisms operate within the lineage to generate neuronal diversity in an unprecedented fashion.

}, issn = {1097-4199}, doi = {10.1016/j.neuron.2011.12.018}, author = {Kao, Chih-Fei and Yu, Hung-Hsiang and He, Yisheng and Kao, Jui-Chun 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 {4287, title = {Birth time/order-dependent neuron type specification.}, journal = {Current Opinion in Neurobiology}, volume = {20}, year = {2010}, month = {2010 Feb}, pages = {14-21}, abstract = {

Neurons derived from the same progenitor may acquire different fates according to their birth timing/order. To reveal temporally guided cell fates, we must determine neuron types as well as their lineage relationships and times of birth. Recent advances in genetic lineage analysis and fate mapping are facilitating such studies. For example, high-resolution lineage analysis can identify each sequentially derived neuron of a lineage and has revealed abrupt temporal identity changes in diverse Drosophila neuronal lineages. In addition, fate mapping of mouse neurons made from the same pool of precursors shows production of specific neuron types in specific temporal patterns. The tools used in these analyses are helping to further our understanding of the genetics of neuronal temporal identity.

}, keywords = {Animals, Cell Lineage, Drosophila, Mice, Neurogenesis, Neurons, Time Factors}, issn = {1873-6882}, doi = {10.1016/j.conb.2009.10.017}, author = {Kao, Chih-Fei and Lee, Tzumin} } @article {783, title = {A complete developmental sequence of a Drosophila neuronal lineage as revealed by twin-spot MARCM.}, journal = {PLoS Biology}, volume = {8}, year = {2010}, month = {2010 Aug 24}, abstract = {

Drosophila brains contain numerous neurons that form complex circuits. These neurons are derived in stereotyped patterns from a fixed number of progenitors, called neuroblasts, and identifying individual neurons made by a neuroblast facilitates the reconstruction of neural circuits. An improved MARCM (mosaic analysis with a repressible cell marker) technique, called twin-spot MARCM, allows one to label the sister clones derived from a common progenitor simultaneously in different colors. It enables identification of every single neuron in an extended neuronal lineage based on the order of neuron birth. Here we report the first example, to our knowledge, of complete lineage analysis among neurons derived from a common neuroblast that relay olfactory information from the antennal lobe (AL) to higher brain centers. By identifying the sequentially derived neurons, we found that the neuroblast serially makes 40 types of AL projection neurons (PNs). During embryogenesis, one PN with multi-glomerular innervation and 18 uniglomerular PNs targeting 17 glomeruli of the adult AL are born. Many more PNs of 22 additional types, including four types of polyglomerular PNs, derive after the neuroblast resumes dividing in early larvae. Although different offspring are generated in a rather arbitrary sequence, the birth order strictly dictates the fate of each post-mitotic neuron, including the fate of programmed cell death. Notably, the embryonic progenitor has an altered temporal identity following each self-renewing asymmetric cell division. After larval hatching, the same progenitor produces multiple neurons for each cell type, but the number of neurons for each type is tightly regulated. These observations substantiate the origin-dependent specification of neuron types. Sequencing neuronal lineages will not only unravel how a complex brain develops but also permit systematic identification of neuron types for detailed structure and function analysis of the brain.

}, keywords = {Animals, Brain, Cell Lineage, Clone Cells, Drosophila, Genetic Techniques, Mosaicism, Neurogenesis, Neurons, Olfactory Pathways}, issn = {1545-7885}, doi = {10.1371/journal.pbio.1000461}, author = {Yu, Hung-Hsiang and Kao, Chih-Fei and He, Yisheng and Ding, Peng and Kao, Jui-Chun 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} }