Journal
DEVELOPMENT
Volume 145, Issue 18, Pages -Publisher
COMPANY BIOLOGISTS LTD
DOI: 10.1242/dev.167775
Keywords
Genetic engineering; Site-specific recombinase (SSR); Nigri-nox; Fate mapping; Cardiac valve development; Genetic engineering; Site-specific recombinase (SSR); Nigri-nox; Fate mapping; Cardiac valve development
Categories
Funding
- National Key Research and Development Program of China [2016YFC1300600, 2017YFC1001303, 2018YFA0107900, 2018YFA0108100]
- Strategic Priority Research Program of the Chinese Academy of Sciences (CAS) [XDB19000000, XDA16020204]
- National Science Foundation of China [31730112, 91639302, 31625019, 81761138040, 31571503, 31501172, 31601168, 31701292, 91749122, 81872241, 81872132, 31801215]
- Youth Innovation Promotion Association of the Chinese Academy of Sciences [2015218, 2060299]
- Key Project of Frontier Sciences of the Chinese Academy of Sciences [QYZDB-SSW-SMC003]
- International Cooperation Fund of the Chinese Academy of Sciences
- Shanghai Science and Technology Commission [17ZR1449600, 17ZR1449800]
- Program for Guangdong Introducing Innovative and Entrepreneurial Teams [2017ZT07S347]
- Shanghai Yangfan Project [16YF1413400, 18YF1427600]
- Shanghai Rising-Star Program [15QA1404300]
- China Postdoctoral Science Foundation [2016\M600337, 2017\M611634, 2017\M621552, 2016\H0042]
- China Postdoctoral Innovative Talent Support Program [BX201700267]
- China Young Talents Lift Engineering [YESS20160050, 2017QNRC001]
- AstraZeneca
- Boehringer Ingelheim
- Sanofi-SIBS Fellowship
- Royal Society-Newton Advanced Fellowship [NA170109]
- Research Council of Hong Kong [04110515, 14111916, C4024-16W]
- Health and Medical Research Fund [03140346, 04152566]
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In vivo genomic engineering is instrumental for studying developmental biology and regenerative medicine. Development of novel systems with more site-specific recombinases (SSRs) that complement with the commonly used Cre-loxP would be valuable for more precise lineage tracing and genome editing. Here, we introduce a new SSR system via Nigri-nox. By generating tissue-specific Nigri knock-in and its responding nox reporter mice, we show that the Nigri-nox system works efficiently in vivo by targeting specific tissues. As a new orthogonal system to Cre-loxP, Nigri-nox provides an additional control of genetic manipulation. We also demonstrate how the two orthogonal systems Nigri-nox and Cre-loxP could be used simultaneously to map the cell fate of two distinct developmental origins of cardiac valve mesenchyme in the mouse heart, providing dynamics of cellular contribution from different origins for cardiac valve mesenchyme during development. This work provides a proofof-principle application of the Nigri-nox system for in vivo mouse genomic engineering. Coupled with other SSR systems, Nigri-nox would be valuable for more precise delineation of origins and cell fates during development, diseases and regeneration.
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