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Genomic analyses reveal FoxG as an upstream regulator of wnt1 required for posterior identity specification in planarians

View ORCID ProfileE. Pascual-Carreras, M. Marín-Barba, S. Castillo-Lara, P. Coronel-Córdoba, View ORCID ProfileM.S. Magri, G.N. Wheeler, View ORCID ProfileJ.F. Abril, View ORCID ProfileJ.L. Gomez-Skarmeta, View ORCID ProfileE. Saló, View ORCID ProfileT. Adell
doi: https://doi.org/10.1101/2020.12.08.416008
E. Pascual-Carreras
1Department of Genetics, Microbiology and Statistics, Universitat de Barcelona (UB) & Institute of Biomedicine of Universitat de Barcelona (IBUB), Barcelona, Spain
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M. Marín-Barba
3School of Biological Sciences, University of East Anglia, Norwich Research Park, Norwich, UK
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S. Castillo-Lara
1Department of Genetics, Microbiology and Statistics, Universitat de Barcelona (UB) & Institute of Biomedicine of Universitat de Barcelona (IBUB), Barcelona, Spain
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P. Coronel-Córdoba
1Department of Genetics, Microbiology and Statistics, Universitat de Barcelona (UB) & Institute of Biomedicine of Universitat de Barcelona (IBUB), Barcelona, Spain
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M.S. Magri
2Centro Andaluz de Biología del Desarollo (CABD), Universidad Pablo de Olavide, Sevilla, Spain
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G.N. Wheeler
3School of Biological Sciences, University of East Anglia, Norwich Research Park, Norwich, UK
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J.F. Abril
1Department of Genetics, Microbiology and Statistics, Universitat de Barcelona (UB) & Institute of Biomedicine of Universitat de Barcelona (IBUB), Barcelona, Spain
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J.L. Gomez-Skarmeta
2Centro Andaluz de Biología del Desarollo (CABD), Universidad Pablo de Olavide, Sevilla, Spain
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  • ORCID record for J.L. Gomez-Skarmeta
E. Saló
1Department of Genetics, Microbiology and Statistics, Universitat de Barcelona (UB) & Institute of Biomedicine of Universitat de Barcelona (IBUB), Barcelona, Spain
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  • For correspondence: esalo@ub.edu tadellc@ub.edu
T. Adell
1Department of Genetics, Microbiology and Statistics, Universitat de Barcelona (UB) & Institute of Biomedicine of Universitat de Barcelona (IBUB), Barcelona, Spain
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  • For correspondence: esalo@ub.edu tadellc@ub.edu
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Abstract

Embryonic specification of the first body axis requires the formation of an Organizer, a group of cells with the ability to instruct fates in the surrounding tissue. The existence of organizing regions in adults, i.e. during regeneration, which also requires patterning of new tissues, remains unstudied. To that aim, we study regeneration in planarians, flatworms that can regenerate any missing structure, even the head, in a few days. In planarians, as described in embryonic models, the cWNT pathway specifies the anterior-posterior axis. During the first 12-24h after amputation both wnt1 and notum (a Wnt inhibitor) are expressed in any wound, but 48 hours later they become restricted to posterior or anterior facing wounds, forming the anterior and the posterior organizers, respectively. In this study we undertook a genomic approach to further understand the mechanism that triggers the early expression of wnt1 and the specification of the posterior identity. Through ATAC-sequencing and CHIPmentation techniques we uncovered Cis-Regulatory Elements of Schmidtea mediterranea genome and analyzed them in notum and wnt1 (RNAi) animals. The result shows that already at 12 hours after amputation the chromatin structure of the wounds has changed its conformation according to the polarity of the pre-existing tissue. Analysing the DNA binding motives present in the proximal regulatory regions of genes down-regulated after wnt1 (RNAi) we found a few genes containing a TCF binding site, which include posterior Homeobox genes and chromatin remodelling proteins, suggesting that those are direct targets of the cWNT pathway and the responsible to trigger the expression of the posterior effectors. Furthermore, we have identified FoxG as an up-stream regulator of wnt1 transcription, probably though binding to an enhancer found in its first intron. Silencing of foxG inhibits the early phase of wnt1 expression and phenocopies the wnt1 (RNAi) phenotype, indicating its early role in specifying posterior versus anterior identity. Moreover, we have created a new open platform to interpret all transcriptomic and genomic results obtained (https://compgen.bio.ub.edu/PlanNET/planexp).

Competing Interest Statement

The authors have declared no competing interest.

Footnotes

  • https://compgen.bio.ub.edu/PlanNET/planexp

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license.
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Posted December 09, 2020.
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Genomic analyses reveal FoxG as an upstream regulator of wnt1 required for posterior identity specification in planarians
E. Pascual-Carreras, M. Marín-Barba, S. Castillo-Lara, P. Coronel-Córdoba, M.S. Magri, G.N. Wheeler, J.F. Abril, J.L. Gomez-Skarmeta, E. Saló, T. Adell
bioRxiv 2020.12.08.416008; doi: https://doi.org/10.1101/2020.12.08.416008
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Genomic analyses reveal FoxG as an upstream regulator of wnt1 required for posterior identity specification in planarians
E. Pascual-Carreras, M. Marín-Barba, S. Castillo-Lara, P. Coronel-Córdoba, M.S. Magri, G.N. Wheeler, J.F. Abril, J.L. Gomez-Skarmeta, E. Saló, T. Adell
bioRxiv 2020.12.08.416008; doi: https://doi.org/10.1101/2020.12.08.416008

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