AbstractCrucial parts of the sense organs arise from common precursors in the pre-placodal region (PPR). The PPR is marked by the factors Six1/4 and Eya2, which are both sufficient and required for PPR properties. Their induction requires signals from the head and prechordal mesoderm and the adjacent neural plate has also been implicated. However, their relative contribution has not been established.
Using a differential screen new PPR regulators as well as genes, which define the PPR spatially, were identified. Using these I dissected the transcriptional hierarchy downstream of PPR-inducing tissues. Both lateral head and prechordal mesoderm initially induce the same set of genes, but these responses diverge later, providing some rostro- caudal bias. However, grafts of neural plate alone do not induce a PPR, but provides further regional identity. Combining mesodermal tissue with neural plate tissue in an axial homotypic manner induces placodes with distinct identities, relative to the axial origin of the inducing tissue, while heterotypic grafts resulted in undefined domains. These results suggest a model for placode induction: initial induction generates a generic state, from which cells diverge under the influence of local signals.
The PPR is positioned by FGF and Wnt and Bmp antagonists emanating from the underlying mesoderm. To determine the genes regulated by each signal I combined tissue grafts, inhibitors and agonists of each pathway and determined the changes of gene expression in the responding tissue over time. This analysis reveals that all three pathways are required for PPR formation. FGF signalling appears to act early to specify a common domain, with some input from BMP antagonists, with later PPR regulation requiring combined input from all three signal factors.
|Date of Award
|1 Feb 2016
|Andrea Streit (Supervisor)