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A novel Axin2 knock-in mouse model for visualization and lineage tracing of WNT/CTNNB1 responsive cells.


ABSTRACT: Wnt signal transduction controls tissue morphogenesis, maintenance and regeneration in all multicellular animals. In mammals, the WNT/CTNNB1 (Wnt/?-catenin) pathway controls cell proliferation and cell fate decisions before and after birth. It plays a critical role at multiple stages of embryonic development, but also governs stem cell maintenance and homeostasis in adult tissues. However, it remains challenging to monitor endogenous WNT/CTNNB1 signaling dynamics in vivo. Here, we report the generation and characterization of a new knock-in mouse strain that doubles as a fluorescent reporter and lineage tracing driver for WNT/CTNNB1 responsive cells. We introduced a multi-cistronic targeting cassette at the 3' end of the universal WNT/CTNNB1 target gene Axin2. The resulting knock-in allele expresses a bright fluorescent reporter (3xNLS-SGFP2) and a doxycycline-inducible driver for lineage tracing (rtTA3). We show that the Axin2P2A-rtTA3-T2A-3xNLS-SGFP2 strain labels WNT/CTNNB1 responsive cells at multiple anatomical sites during different stages of embryonic and postnatal development. It faithfully reports the subtle and dynamic changes in physiological WNT/CTNNB1 signaling activity that occur in vivo. We expect this mouse strain to be a useful resource for biologists who want to track and trace the location and developmental fate of WNT/CTNNB1 responsive stem cells in different contexts.

SUBMITTER: van de Moosdijk AAA 

PROVIDER: S-EPMC7539917 | biostudies-literature | 2020 Sep

REPOSITORIES: biostudies-literature

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A novel Axin2 knock-in mouse model for visualization and lineage tracing of WNT/CTNNB1 responsive cells.

van de Moosdijk Anoeska Agatha Alida AAA   van de Grift Yorick Bernardus Cornelis YBC   de Man Saskia Madelon Ada SMA   Zeeman Amber Lisanne AL   van Amerongen Renée R  

Genesis (New York, N.Y. : 2000) 20200709 9


Wnt signal transduction controls tissue morphogenesis, maintenance and regeneration in all multicellular animals. In mammals, the WNT/CTNNB1 (Wnt/β-catenin) pathway controls cell proliferation and cell fate decisions before and after birth. It plays a critical role at multiple stages of embryonic development, but also governs stem cell maintenance and homeostasis in adult tissues. However, it remains challenging to monitor endogenous WNT/CTNNB1 signaling dynamics in vivo. Here, we report the gen  ...[more]

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