Characterization of the Temporal Dynamics of Wnt-mediated Posteriorization of the Vertebrate Neural Plate

Date

2019-08

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Abstract

The vertebrate central nervous system is divided into a series of functional domains along the AP axis; forebrain, midbrain, hindbrain, and spinal cord. Failure to properly pattern the AP axis has been associated with a range of neuropathologies including schizophrenia and autism. In recent years, there have been numerous findings that have challenged dogmatic beliefs in how the AP axis is established during embryogenesis.\par

After induction, the AP axis of the neural plate is established via several posteriorizing morphogens, including \textit{wnt8a}. Wnt8a is secreted from the margin and forms a signaling gradient. The current dogma suggests that this signaling gradient is achieved by diffusion. Recent evidence supports an alternative model where Wnt8a is transported along cellular protrusions called filopodia. The filopodial model introduces several inconsistencies that must be resolved.\par

Here we provide evidence that primary Wnt-mediated posteriorization of the neural plate occurs in a narrow window of time between 4.6 hpf and 7 hpf. The interpretation of this signal by the neural plate is complex and outcomes of these signals are sometimes not detected until several hours later. A secondary phase of Wnt-mediated posteriorization is regulated by Wnts expressed in the neural plate. These findings provide rationale for how filopodial-mediated Wnt-signaling occurs early in epiboly while the neural plate is still in range. Additionally our findings establish new temporal elements to the Wnt-mediated posteriorization paradigm, showing that the neural plate responds dynamically to Wnt signaling both in regards to competency to Wnt as well as the time it takes for Wnt signaling to affect transcription. Together these findings provide important steps to redefining the Wnt-signaling paradigm in lieu of recent challenges to the previous model.

Description

Keywords

Developmental, Brain, AP patterning, Zebrafish

Citation

Portions of this document appear in: Green, David, Amy E. Whitener, Saurav Mohanty, and Arne C. Lekven. "Vertebrate nervous system posteriorization: Grading the function of Wnt signaling." Developmental Dynamics 244, no. 3 (2015): 507-512.