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Fishell, Gordon

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Fishell

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Fishell, Gordon

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2020 - 20212

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Author's Publications: search.filters.isAuthorOfPublication.2bcf1fd0-7221-47ab-9552-1b53444b830c

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    Single-cell delineation of lineage and genetic identity in the mouse brain
    (Springer Science and Business Media LLC, 2021-12-15) Bandler, Rachel; Vitali, Ilaria; Delgado, Ryan; Ho, May; Dvoretskova, Elena; Ibarra Molinas, Josue; Frazel, Paul; Mohammadkhani, Maesoumeh; Machold, Robert; Maedler, Sophia; Liddelow, Shane; Nowakowski, Tomasz; Fishell, Gordon; Mayer, Christian
    During neurogenesis, mitotic progenitor cells lining the ventricles of the embryonic mouse brain undergo their final rounds of cell division, giving rise to a wide spectrum of postmitotic neurons and glia. The link between developmental lineage and cell type diversity remains an open question. Here we used massively parallel tagging of progenitors to track clonal relationships and transcriptomic signatures during murine forebrain development. We quantified clonal divergence and convergence across all major cell classes postnatally, and found diverse types of GABAergic neurons that share a common lineage. Divergence of GABAergic clones occurred during embryogenesis upon cell-cycle exit, suggesting that differentiation into subtypes is initiated as a lineage-dependent processes at the progenitor cell level.
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    Viral Manipulation of Functionally Distinct Interneurons in Mice, Non-Human Primates and Humans
    (Cold Spring Harbor Laboratory, 2020-08-17) Vormstein-Schneider, Douglas; Lin, Jessica; Pelkey, Kenneth; Chittajallu, Ramesh; Guo, Baolin; Garcia, Mario Arias; Allaway, Kathryn; Sakopoulos, Sofia; Schneider, Gates; Stevenson, Olivia; Vergara Cobos, Josselyn; Sharma, Jitendra; Zhang, Qiangge; Franken, Tom; Smith, Jared; Ali Ibrahim Marosh, Leena; Mastro, Kevin; Sabri, Ehsan; Huang, Shuhan; Favuzzi, Emilia; Burbridge, Timothy; Xu, Qing; Guo, Lihua; Vogel, Ian; Sanchez, Vanessa; Saldi, Giuseppe; Gorissen, Bram; Yuan, Xiaoqing; Zaghloul, Kareem A.; Devinsky, Orrin; Sabatini, Bernardo; Batista-Brito, Renata; Reynolds, John; Feng, Guoping; Fu, Zhanyan; McBain, Chris; Fishell, Gordon; Dimidschstein, Jordane
    Recent success in identifying gene regulatory elements in the context of recombinant adeno-associated virus vectors have enabled cell type-restricted gene expression. However, within the cerebral cortex these tools are presently limited to broad classes of neurons. To overcome this limitation, we developed a strategy that led to the identification of multiple novel enhancers to target functionally distinct neuronal subtypes. By investigating the regulatory landscape of the disease gene Scn1a, we identified enhancers that target the breadth of its expression, including two that are selective for parvalbumin and vasoactive intestinal peptide cortical interneurons. Demonstrating the functional utility of these elements, we found that the PV-specific enhancer allowed for the selective targeting and manipulation of these neurons across species, from mice to humans. Finally, we demonstrate that our selection method is generalizable to other genes and characterize four additional PV-specific enhancers with exquisite specificity for distinct regions of the brain. Altogether, these viral tools can be used for cell-type specific circuit manipulation and hold considerable promise for use in therapeutic interventions.