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3 Publications

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    09/02/22 | Tracing and Manipulating Drosophila Cell Lineages Based on CRISPR: CaSSA and CLADES.
    Garcia-Marques J, Lee T
    Methods in Molecular Biology. 2022 Sep 02;2540:201-217. doi: 10.1007/978-1-0716-2541-5_9

    Cell lineage defines the mitotic connection between cells that make up an organism. Mapping these connections in relation to cell identity offers an extraordinary insight into the mechanisms underlying normal and pathological development. The analysis of molecular determinants involved in the acquisition of cell identity requires gaining experimental access to precise parts of cell lineages. Recently, we have developed CaSSA and CLADES, a new technology based on CRISPR that allows targeting and labeling specific lineage branches. Here we discuss how to better exploit this technology for lineage studies in Drosophila, with an emphasis on neuronal specification.

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    06/12/22 | Metamorphosis of memory circuits in Drosophila reveal a strategy for evolving a larval brain.
    James W. Truman , Jacquelyn Price , Rosa L. Miyares , Tzumin Lee
    bioRxiv. 2022 Jun 12:. doi: 10.1101/2022.06.09.495452

    Insects like Drosophila produce a second brain adapted to the form and behavior of a larva. Neurons for both larval and adult brains are produced by the same stem cells (neuroblasts) but the larva possesses only the earliest born neurons produced from each. To understand how a functional larval brain is made from this reduced set of neurons, we examined the origins and metamorphic fates of the neurons of the larval and adult mushroom body circuits. The adult mushroom body core is built sequentially of γ Kenyon cells, that form a medial lobe, followed by α’β’, and αβ Kenyon cells that form additional medial lobes and two vertical lobes. Extrinsic input (MBINs) and output (MBONs) neurons divide this core into computational compartments. The larval mushroom body contains only γ neurons. Its medial lobe compartments are roughly homologous to those of the adult and same MBONs are used for both. The larval vertical lobe, however, is an analogous “facsimile” that uses a larval-specific branch on the γ neurons to make up for the missing α’β’, and αβ neurons. The extrinsic cells for the facsimile are early-born neurons that trans-differentiate to serve a mushroom body function in the larva and then shift to other brain circuits in the adult. These findings are discussed in the context of the evolution of a larval brain in insects with complete metamorphosis.

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    05/23/22 | Hormone-controlled changes in the differentiation state of post-mitotic neurons.
    Lai Y, Miyares RL, Liu L, Chu S, Lee T, Yu H
    Current Biology. 2022 May 23;32(10):2341-2348. doi: 10.1016/j.cub.2022.04.027

    While we think of neurons as having a fixed identity, many show spectacular plasticity. Metamorphosis drives massive changes in the fly brain; neurons that persist into adulthood often change in response to the steroid hormone ecdysone. Besides driving remodeling, ecdysone signaling can also alter the differentiation status of neurons. The three sequentially born subtypes of mushroom body (MB) Kenyon cells (γ, followed by α'/β', and finally α/β) serve as a model of temporal fating. γ neurons are also used as a model of remodeling during metamorphosis. As γ neurons are the only functional Kenyon cells in the larval brain, they serve the function of all three adult subtypes. Correspondingly, larval γ neurons have a similar morphology to α'/β' and α/β neurons-their axons project dorsally and medially. During metamorphosis, γ neurons remodel to form a single medial projection. Both temporal fate changes and defects in remodeling therefore alter γ-neuron morphology in similar ways. Mamo, a broad-complex, tramtrack, and bric-à-brac/poxvirus and zinc finger (BTB/POZ) transcription factor critical for temporal specification of α'/β' neurons, was recently described as essential for γ remodeling. In a previous study, we noticed a change in the number of adult Kenyon cells expressing γ-specific markers when mamo was manipulated. These data implied a role for Mamo in γ-neuron fate specification, yet mamo is not expressed in γ neurons until pupariation, well past γ specification. This indicates that mamo has a later role in ensuring that γ neurons express the correct Kenyon cell subtype-specific genes in the adult brain.

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