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Analysis of the wnt1 regulatory chromosomal landscape

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Abstract

One of the earliest patterning events in the vertebrate neural plate is the specification of mes/r1, the territory comprising the prospective mesencephalon and the first hindbrain rhombomere. Within mes/r1, an interface of gene expression defines the midbrain–hindbrain boundary (MHB), a lineage restriction that separates the mesencephalon and rhombencephalon. wnt1 is critical to mes/r1 development and functions within the MHB as a component of the MHB gene regulatory network (GRN). Despite its importance to these critical and early steps of vertebrate neurogenesis, little is known about the factors responsible for wnt1 transcriptional regulation. In the zebrafish, wnt1 and its neighboring paralog, wnt10b, are expressed in largely overlapping patterns, suggesting co-regulation. To understand wnt1 and wnt10b transcriptional control, we used a comparative genomics approach to identify relevant enhancers. We show that the wnt1-wnt10b locus contains multiple cis-regulatory elements that likely interact to generate the wnt1 and wnt10b expression patterns. Two of 11 conserved enhancers tested show activity restricted to the midbrain and MHB, an activity that is conserved in the distantly related spotted gar orthologous elements. Three non-conserved elements also play a likely role in wnt1 regulation. The identified enhancers display dynamic modes of chromatin accessibility, suggesting controlled deployment during embryogenesis. Our results suggest that the control of wnt1 and wnt10b expression is under complex regulation involving the interaction of multiple enhancers.

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Acknowledgements

The authors thank Dr. Jo-Ann Fleming for thoughtful discussions regarding this work and for fish care and Dr. Laura Beaster-Jones for discussions and assistance during various stages of this project. We are also grateful to Dr. Ingo Braasch and Dr. John Postlethwait for kindly providing spotted gar samples.

Funding

This work was supported in part by NIH grant 1R01NS088564.

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Authors and Affiliations

  1. Department of Biology and Biochemistry, University of Houston, Houston, TX, 77204-5001, USA

    Arne C. Lekven & David G. Green

  2. Department of Biology, Texas A&M University, College Station, TX, 77843-3258, USA

    Arne C. Lekven, Craig J. Lilie & Avantika Singh

  3. Department of Biomedical Engineering, Texas A&M University, College Station, TX, 77843-3120, USA

    Holly C. Gibbs & Alvin T. Yeh

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  1. Arne C. Lekven
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Correspondence to Arne C. Lekven.

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Communicated by Caroline Brennan

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Lekven, A.C., Lilie, C.J., Gibbs, H.C. et al. Analysis of the wnt1 regulatory chromosomal landscape. Dev Genes Evol 229, 43–52 (2019). https://doi.org/10.1007/s00427-019-00629-5

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