Wnt signaling in fate determination of retinal precursors
Abstract: The fish retina provides an ideal experimental environment with continuous, life-long proliferation and differentiation within a domain expressing all components of the canonical Wnt signaling pathway. Wnt signaling has been proposed to act on both, cell proliferation as well as progenitor differentiation during the life-long retinal neurogenesis in fish. In in vitro assays Wnt was shown to direct the cell division plane and hence potentially directly governing cell fate decisions. We plan to target single cells in vivo in the fish retina to precisely address the role of Wnt in directing cell proliferation versus cell fate decisions with a cell biological readout. Our questions relate to the instructive input of a localized Wnt source directing asymmetric divisions of retinal precursors. We will address how canonical Wnt signaling downstream of the receptor mediates the signals that ultimately result in an asymmetric distribution of cell fates. To do so we follow two different approaches both combining clonal genetics, advanced imaging and mathematical modeling: We will establish a local Wnt gradient in the retina in a conditional manner by localized induction of Wnt expression and secretion in specific cells. We will study mitotic features as well as the fates of the cells exposed to different concentrations of the Wnt gradient and provide quantitative data to the morphogen modeling project. In parallel, we will specifically study the role of Wnt signaling in the differentiating lineage of retinal progenitors. In collaboration with the modeling project we will target our conditional tools to trigger constitutively active or dominant negative Wnt signaling components in individual retinal precursors to address competence and concentration dependent fate decisions.