Zorn Aaron M.

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Aaron M.

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  • Article
    Normal table of Xenopus development: a new graphical resource
    (The Company of Biologists, 2022-07-14) Zahn, Natalya ; James-Zorn, Christina ; Ponferrada, Virgilio G. ; Adams, Dany S. ; Grzymkowski, Julia ; Buchholz, Daniel R. ; Nascone-Yoder, Nanette M. ; Horb, Marko E. ; Moody, Sally A. ; Vize, Peter D. ; Zorn, Aaron M.
    Normal tables of development are essential for studies of embryogenesis, serving as an important resource for model organisms, including the frog Xenopus laevis. Xenopus has long been used to study developmental and cell biology, and is an increasingly important model for human birth defects and disease, genomics, proteomics and toxicology. Scientists utilize Nieuwkoop and Faber's classic ‘Normal Table of Xenopus laevis (Daudin)’ and accompanying illustrations to enable experimental reproducibility and reuse the illustrations in new publications and teaching. However, it is no longer possible to obtain permission for these copyrighted illustrations. We present 133 new, high-quality illustrations of X. laevis development from fertilization to metamorphosis, with additional views that were not available in the original collection. All the images are available on Xenbase, the Xenopus knowledgebase (http://www.xenbase.org/entry/zahn.do), for download and reuse under an attributable, non-commercial creative commons license. Additionally, we have compiled a ‘Landmarks Table’ of key morphological features and marker gene expression that can be used to distinguish stages quickly and reliably (https://www.xenbase.org/entry/landmarks-table.do). This new open-access resource will facilitate Xenopus research and teaching in the decades to come.
  • Article
    Sox17 and ß-catenin co-occupy Wnt-responsive enhancers to govern the endoderm gene regulatory network
    (eLife Sciences Publications, 2020-09-07) Mukherjee, Shreyasi ; Chaturvedi, Praneet ; Rankin, Scott A. ; Fish, Margaret B. ; Wlizla, Marcin ; Paraiso, Kitt D. ; MacDonald, Melissa ; Chen, Xiaoting ; Weirauch, Matthew T. ; Blitz, Ira L. ; Cho, Ken W. Y. ; Zorn, Aaron M.
    Lineage specification is governed by gene regulatory networks (GRNs) that integrate the activity of signaling effectors and transcription factors (TFs) on enhancers. Sox17 is a key transcriptional regulator of definitive endoderm development, and yet, its genomic targets remain largely uncharacterized. Here, using genomic approaches and epistasis experiments, we define the Sox17-governed endoderm GRN in Xenopus gastrulae. We show that Sox17 functionally interacts with the canonical Wnt pathway to specify and pattern the endoderm while repressing alternative mesectoderm fates. Sox17 and β-catenin co-occupy hundreds of key enhancers. In some cases, Sox17 and β-catenin synergistically activate transcription apparently independent of Tcfs, whereas on other enhancers, Sox17 represses β-catenin/Tcf-mediated transcription to spatially restrict gene expression domains. Our findings establish Sox17 as a tissue-specific modifier of Wnt responses and point to a novel paradigm where genomic specificity of Wnt/β-catenin transcription is determined through functional interactions between lineage-specific Sox TFs and β-catenin/Tcf transcriptional complexes. Given the ubiquitous nature of Sox TFs and Wnt signaling, this mechanism has important implications across a diverse range of developmental and disease contexts.
  • Article
    Maximizing CRISPR/Cas9 phenotype penetrance applying predictive modeling of editing outcomes in Xenopus and zebrafish embryos
    (Nature Research, 2020-09-04) Naert, Thomas ; Tulkens, Dieter ; Edwards, Nicole A. ; Carron, Marjolein ; Shaidani, Nikko-Ideen ; Wlizla, Marcin ; Boel, Annekatrien ; Demuynck, Suzan ; Horb, Marko E. ; Coucke, Paul ; Willaert, Andy ; Zorn, Aaron M. ; Vleminckx, Kris
    CRISPR/Cas9 genome editing has revolutionized functional genomics in vertebrates. However, CRISPR/Cas9 edited F0 animals too often demonstrate variable phenotypic penetrance due to the mosaic nature of editing outcomes after double strand break (DSB) repair. Even with high efficiency levels of genome editing, phenotypes may be obscured by proportional presence of in-frame mutations that still produce functional protein. Recently, studies in cell culture systems have shown that the nature of CRISPR/Cas9-mediated mutations can be dependent on local sequence context and can be predicted by computational methods. Here, we demonstrate that similar approaches can be used to forecast CRISPR/Cas9 gene editing outcomes in Xenopus tropicalis, Xenopus laevis, and zebrafish. We show that a publicly available neural network previously trained in mouse embryonic stem cell cultures (InDelphi-mESC) is able to accurately predict CRISPR/Cas9 gene editing outcomes in early vertebrate embryos. Our observations can have direct implications for experiment design, allowing the selection of guide RNAs with predicted repair outcome signatures enriched towards frameshift mutations, allowing maximization of CRISPR/Cas9 phenotype penetrance in the F0 generation.