RecV recombinase system for in vivo targeted optogenomic modifications of single cells or cell populations

Shenqin Yao, Peng Yuan, Ben Ouellette, Thomas Zhou, Marty Mortrud, Pooja Balaram, Soumya Chatterjee, Yun Wang, Tanya L. Daigle, Bosiljka Tasic, Xiuli Kuang, Hui Gong, Qingming Luo, Shaoqun Zeng, Andrew Curtright, Ajay Dhaka, Anat Kahan, Viviana Gradinaru, Radosław Chrapkiewicz, Mark SchnitzerHongkui Zeng, Ali Cetin*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

34 Scopus citations

Abstract

Brain circuits comprise vast numbers of interconnected neurons with diverse molecular, anatomical and physiological properties. To allow targeting of individual neurons for structural and functional studies, we created light-inducible site-specific DNA recombinases based on Cre, Dre and Flp (RecVs). RecVs can induce genomic modifications by one-photon or two-photon light induction in vivo. They can produce targeted, sparse and strong labeling of individual neurons by modifying multiple loci within mouse and zebrafish genomes. In combination with other genetic strategies, they allow intersectional targeting of different neuronal classes. In the mouse cortex they enable sparse labeling and whole-brain morphological reconstructions of individual neurons. Furthermore, these enzymes allow single-cell two-photon targeted genetic modifications and can be used in combination with functional optical indicators with minimal interference. In summary, RecVs enable spatiotemporally precise optogenomic modifications that can facilitate detailed single-cell analysis of neural circuits by linking genetic identity, morphology, connectivity and function.

Original languageEnglish
Pages (from-to)422-429
Number of pages8
JournalNature Methods
Volume17
Issue number4
DOIs
StatePublished - 1 Apr 2020
Externally publishedYes

Bibliographical note

Publisher Copyright:
© 2020, The Author(s), under exclusive licence to Springer Nature America, Inc.

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