An embryonic system to assess Wnt transcriptional targets: Comparing opposing Wnt pathways and transcriptional activation and repression.

During animal development, signals determine and organize a vast number of complex 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 -catenin/TCF transcriptional complex. Here we report an in vivo Drosophila assay that we 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 a specific set of genes downstream of both -catenin and TCF with an additional group of genes regulated by Wnt. 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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Suresh J, Harmston N, Lim KK, Kaur P, Jin HJ, Lusk JB, Petretto E, Tolwinski NS