An embryonic system to assess direct and indirect Wnt transcriptional targets

评估直接和间接 Wnt 转录靶标的胚胎系统

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作者:Jahnavi Suresh, Nathan Harmston, Ka Keat Lim, Prameet Kaur, Helen Jingshu Jin, Jay B Lusk, Enrico Petretto, Nicholas S Tolwinski

Abstract

During animal development, complex signals determine and organize a vast number of tissues using a very small number of signal transduction pathways. These developmental signaling pathways determine cell fates through a coordinated transcriptional response that remains poorly understood. The Wnt pathway is involved in a variety of these cellular functions, and its signals are transmitted in part through a β-catenin/TCF transcriptional complex. Here we report an in vivo Drosophila assay that can be used to distinguish between activation, de-repression and repression of transcriptional responses, separating upstream and downstream pathway activation and canonical/non-canonical Wnt signals in embryos. We find specific sets of genes downstream of both β-catenin and TCF with an additional group of genes regulated by Wnt, while the non-canonical Wnt4 regulates a separate cohort of genes. We correlate transcriptional changes with phenotypic outcomes of cell differentiation and embryo size, showing our model can be used to characterize developmental signaling compartmentalization in vivo.

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