SCIENCE CHINA Life Sciences, Volume 61 , Issue 9 : 1115-1117(2018) https://doi.org/10.1007/s11427-018-9291-2

Intersectional gene inactivation: there is more to conditional mutagenesis than Cre

More info
  • ReceivedFeb 28, 2018
  • AcceptedMar 15, 2018
  • PublishedMay 18, 2018


There is no abstract available for this article.

Funded by

grants RO1 DE022363 and RO1 DE022378 from the National Institute of Dental and Craniofacial Research.


I thank members of my laboratory for helpful discussions and critical reading of the manuscript. I apologize to colleagues whose work I have been unable to cite due to space limitations. Work in my laboratory is supported by grants RO1 DE022363 and RO1 DE022778 from the National Institute of Dental and Craniofacial Research.

Interest statement

The author declares that he has no conflict of interest.


[1] Anastassiadis K., Fu J., Patsch C., Hu S., Weidlich S., Duerschke K., Buchholz F., Edenhofer F., Stewart A.F.. Dre recombinase, like Cre, is a highly efficient site-specific recombinase in E. coli, mammalian cells and mice. Dis Model Mech, 2009, 2: 508-515 CrossRef PubMed Google Scholar

[2] Attanasio C., Nord A.S., Zhu Y., Blow M.J., Li Z., Liberton D.K., Morrison H., Plajzer-Frick I., Holt A., Hosseini R., et al. Fine tuning of craniofacial morphology by distant-acting enhancers. Science, 2013, 342: 1241006-1241006 CrossRef PubMed Google Scholar

[3] Awatramani R., Soriano P., Rodriguez C., Mai J.J., Dymecki S.M.. Cryptic boundaries in roof plate and choroid plexus identified by intersectional gene activation. Nat Genet, 2003, 35: 70-75 CrossRef PubMed Google Scholar

[4] Ayadi A., Birling M.C., Bottomley J., Bussell J., Fuchs H., Fray M., Gailus-Durner V., Greenaway S., Houghton R., Karp N., et al. Mouse large-scale phenotyping initiatives: overview of the European Mouse Disease Clinic (EUMODIC) and of the Wellcome Trust Sanger Institute Mouse Genetics Project. Mamm Genome, 2012, 23: 600-610 CrossRef PubMed Google Scholar

[5] Barriga, E.H., Trainor, P.A., Bronner, M., and Mayor, R. (2015). Animal models for studying neural crest development: is the mouse different? Development 142, 1555–1560. Google Scholar

[6] Branda C.S., Dymecki S.M.. Talking about a revolution. Dev Cell, 2004, 6: 7-28 CrossRef Google Scholar

[7] Brewer J.R., Molotkov A., Mazot P., Hoch R.V., Soriano P.. Fgfr1 regulates development through the combinatorial use of signaling proteins. Genes Dev, 2015, 29: 1863-1874 CrossRef PubMed Google Scholar

[8] Danielian P.S., Muccino D., Rowitch D.H., Michael S.K., McMahon A.P.. Modification of gene activity in mouse embryos in utero by a tamoxifen-inducible form of Cre recombinase. Curr Biol, 1998, 8: 1323-S2 CrossRef Google Scholar

[9] Gerfen C.R., Paletzki R., Heintz N.. GENSAT BAC Cre-recombinase driver lines to study the functional organization of cerebral cortical and basal ganglia circuits. Neuron, 2013, 80: 1368-1383 CrossRef PubMed Google Scholar

[10] Hermann M., Stillhard P., Wildner H., Seruggia D., Kapp V., Sánchez-Iranzo H., Mercader N., Montoliu L., Zeilhofer H.U., Pelczar P.. Binary recombinase systems for high-resolution conditional mutagenesis. Nucleic Acids Res, 2014, 42: 3894-3907 CrossRef PubMed Google Scholar

[11] Lao Z., Raju G.P., Bai C.B., Joyner A.L.. MASTR: A technique for mosaic mutant analysis with spatial and temporal control of recombination using conditional floxed alleles in mice. Cell Rep, 2012, 2: 386-396 CrossRef PubMed Google Scholar

[12] Legué, E., and Joyner, A.L. (2010). Genetic fate mapping using site-specific recombinases. Methods Enzymol 477, 153-181. Google Scholar

[13] Lewis A.E., Vasudevan H.N., O'Neill A.K., Soriano P., Bush J.O.. The widely used Wnt1-Cre transgene causes developmental phenotypes by ectopic activation of Wnt signaling. Dev Biol, 2013, 379: 229-234 CrossRef PubMed Google Scholar

[14] Prescott S.L., Srinivasan R., Marchetto M.C., Grishina I., Narvaiza I., Selleri L., Gage F.H., Swigut T., Wysocka J.. Enhancer divergence and cis-regulatory evolution in the human and chimp neural crest. Cell, 2015, 163: 68-83 CrossRef PubMed Google Scholar

[15] Raymond C.S., Soriano P.. High-efficiency FLP and ΦC31 site-specific recombination in mammalian cells. PLoS ONE, 2007, 2: e162 CrossRef PubMed ADS Google Scholar

[16] Tallquist M.D., Soriano P.. Cell autonomous requirement for PDGFRalpha in populations of cranial and cardiac neural crest cells. Development, 2003, 130: 507-518 CrossRef Google Scholar

[17] Uslu V.V., Petretich M., Ruf S., Langenfeld K., Fonseca N.A., Marioni J.C., Spitz F.. Long-range enhancers regulating Myc expression are required for normal facial morphogenesis. Nat Genet, 2014, 46: 753-758 CrossRef PubMed Google Scholar

  • Figure 1

    Intersectional gene inactivation. A, Using the example of craniofacial development, an E10.5 embryo includes multiple neural crest cell-derived structures (first panel), including the Lateral Nasal Process (purple), Medial Nasal Process (blue), Maxillary Process (gold) and Mandibular Process (Orange). B, In a hypothetical example, Flpo driven by promoter 1 (top) may be expressed in the Medial- and Lateral Nasal Processes (A, second panel), and Cre driven by promoter 2 (middle) can be expressed in the Medial Nasal and Mandibular Processes (A, third panel); expression of Cre is prevented by a stop sequence flanked by Frt sites. Cre is therefore only expressed in domains where both promoter 1 and promoter 2 are active, resulting in conditional mutagenesis of a conventional floxed allele (bottom) in the Medial Nasal Process alone (A, fourth panel, yellow). Dre or ΦC31o could equally be used instead of Flpo for conditional activation of an appropriately designed Cre allele (containing Rox or AttP/B sites, respectively). Scanning electron micrographs taken from Facebase (https://www.facebase.org/).

Copyright 2020 Science China Press Co., Ltd. 《中国科学》杂志社有限责任公司 版权所有

京ICP备17057255号       京公网安备11010102003388号