Patterning of the neural tube: A 3D computational modelling approach
Sammanfattning: Neurodegenerative diseases such as Parkinson’s can be treated with stem-cell derived specialized neurons. In order to achieve precise directed neural differentiation in vitro we need to understand the gene regulatory mechanisms behind in vivo neural tube patterning. We implement a 3D computational model of brain patterning to simulate this process. The mathematical model is set up by unifying two existing gene regulatory network models for patterning of the dorsoventral and rostrocaudal axes on the basis of WNT-signaling. A custom Python-based simulation tool was implemented in order to accurately simulate reaction-diffusion equations and signaling secretion sources. We discuss the validity of the implemented model and explore its properties in two different geometries. We find a possible correlation between dorsoventral patterning and vesicle formation as well as a segment in which fore-, mid- and hindbrain expression are stacked dorsoventrally. Furthermore, we identify a need for an adaption of one of the networks to signal exposure time. While it is hard to make any specific predictions for in vitro differentiation at this point, we have created a working fundament for future insights using our simulation tool and a more extensive mathematical model.
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