Light-activated Frizzled7 reveals a permissive role of non-canonical wnt signaling in mesendoderm cell migration

Abstract

Non-canonical Wnt signaling plays a central role for coordinated cell polarization and directed migration in metazoan development. While spatiotemporally restricted activation of non-canonical Wnt-signaling drives cell polarization in epithelial tissues, it remains unclear whether such instructive activity is also critical for directed mesenchymal cell migration. Here, we developed a light-activated version of the non-canonical Wnt receptor Frizzled 7 (Fz7) to analyze how restricted activation of non-canonical Wnt signaling affects directed anterior axial mesendoderm (prechordal plate, ppl) cell migration within the zebrafish gastrula. We found that Fz7 signaling is required for ppl cell protrusion formation and migration and that spatiotemporally restricted ectopic activation is capable of redirecting their migration. Finally, we show that uniform activation of Fz7 signaling in ppl cells fully rescues defective directed cell migration in fz7 mutant embryos. Together, our findings reveal that in contrast to the situation in epithelial cells, non-canonical Wnt signaling functions permissively rather than instructively in directed mesenchymal cell migration during gastrulation.

Engineered illumination devices for optogenetic control of cellular signaling dynamics

“…Optogenetic methods have also been recently applied to studies in developmental biology in key model organisms (Johnson & Toettcher 2018). For example, in Drosophila and zebrafish embryos, dynamic control of signaling elucidated the spatiotemporal limits of ERK (Johnson et al 2017; Johnson & Toettcher 2019), Nodal (Sako et al 2016), and Bicoid (Huang et al 2017) patterning and how local modulation of cell migration and contractility drives tissue morphogenesis (Izquierdo et al 2018; Guglielmi et al 2015; Čapek et al 2019). Furthermore, in embryonic stem cell models for mammalian development, we have recently achieved optogenetic control of canonical Wnt signaling and elucidated mechanisms of tissue self-organization during mesendoderm differentiation (Bugaj et al 2013; Repina et al 2019).…”

Optogenetic control of Wnt signaling for modeling early embryogenic patterning with human pluripotent stem cells

“…Light-sensitive protein domains that induce protein-protein interactions or modify protein activity in response to illumination allow optogenetic control of signaling in space and time 36, 37 . Optogenetic strategies have recently been applied for spatiotemporal control of transcription and intracellular signaling in the Drosophila 38–41 1and zebrafish embryo 42–44 . Here, we implement optogenetic control of canonical Wnt signaling to determine whether differential Wnt signaling can model human gastrulation and lead to emergence of organized shape and structure through collective cell rearrangement.…”

A forebrain undivided: Unleashing model organisms to solve the mysteries of holoprosencephaly

“…They will allow us to ask questions originally answered through classical explant‐based methods, but with much more precision. Zebrafish is leading the way in development and application of photoactivatable tools with which to dissect roles of major signaling pathways . The resulting data sets will be complex and computational approaches will be necessary for their analysis, as well as for generating predictions to test in further experiments .…”

“…Zebrafish is leading the way in development and application of photoactivatable tools with which to dissect roles of major signaling pathways. [61][62][63][64][65] The resulting data sets will be complex and computational approaches will be necessary for their analysis, as well as for generating predictions to test in further experiments. 19,20 The power and feasibility of this approach have been demonstrated in recent studies in zebrafish.…”