An embryonic system to assess direct and indirect Wnt transcriptional targets

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.

WNT Signaling in Disease

“…These data suggest that the variants caused by alternative splicing may be a reason to explain the contradictory role of TCF4 [100]. Further studies should elucidate the roles of TCF in cancer and development [101], taking into consideration not only the downstream target genes’ roles, but also the different isoforms that result from alternative splicing. Based on this understanding, more effective therapeutic approaches can be developed to aim for certain isoforms that cause malignant phenotypes.…”

Coupling optogenetics and light-sheet microscopy, a method to study Wnt signaling during embryogenesis

“…Strong Wnt pathway loss of function embryos show a lawn of denticles and are much smaller than wild-type. Restoring some Wnt pathway function rescues the small size phenotype 12 , 31 . The lawn of denticles began getting broader (size of the embryo increased) when light was applied at stage 12 (onset germ band retraction) with some distance developing between the denticle bands (Fig.…”

Coupling optogenetics and light-sheet microscopy, a method to study signal transductionin vivo

“…Strong Wnt pathway loss of function embryos show a lawn of denticles and are much smaller than wild-type. Restoring some Wnt pathway function rescues the small size phenotype 12,30 . The lawn of denticles began getting broader (size of the embryo increased) when light was applied at stage 12 (onset germ band retraction) with some distance developing between the denticle bands (Fig.…”