Temporospatial induction of homeodomain gene cut dictates natural lineage reprogramming
Understanding how cellular identity naturally interconverts with high efficiency and temporospatial precision is crucial for regenerative medicine. Here we revealed a natural midgut-to-renal lineage conversion event during Drosophila metamorphosis and identified the evolutionarily-conserved homeodomain protein Cut as a master switch in this process. A steep Wnt/Wingless morphogen gradient intersects with a pulse of steroid hormone ecdysone to induce cut expression in a subset of midgut progenitors and reprogram them into renal progenitors. Molecularly, ecdysone-induced temporal factor Broad physically interacts with cut enhancer-bound Wnt pathway effector TCF/β-catenin and likely bridges the distant enhancer and promoter region of cut through its self-association. Such long-range enhancer-promoter looping could subsequently trigger timely cut transcription. Our results therefore led us to propose an unexpected poising-and-bridging mechanism whereby spatial and temporal cues intersect, likely via chromatin looping, to turn on a master transcription factor and dictate efficient and precise lineage reprogramming.
All data generated or analysed during this study are included in the manuscript and supporting files.
Article and author information
National Natural Science Foundation of China
- Yan Song
Peking-Tsinghua Center for Life Sciences
- Yan Song
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
- K VijayRaghavan, National Centre for Biological Sciences, Tata Institute of Fundamental Research, India
- Received: November 29, 2017
- Accepted: April 30, 2018
- Accepted Manuscript published: May 1, 2018 (version 1)
- Version of Record published: June 4, 2018 (version 2)
© 2018, Xu et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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