Neural tube patterning : from a minimal model for rostrocaudal patterning toward an integrated 3D model

Summary, in English

Rostrocaudal patterning of the neural tube is a defining event in vertebrate brain development. This process is driven by morphogen gradients which specify the fate of neural progenitor cells, leading to the partitioning of the tube. Although this is extensively studied experimentally, an integrated view of the genetic circuitry is lacking. Here, we present a minimal gene regulatory model for rostrocaudal patterning, whose tristable topology was determined in a data-driven way. Using this model, we identified the repression of hindbrain fate as promising strategy for the improvement of current protocols for the generation of dopaminergic neurons. Furthermore, we combined our model with an established minimal model for dorsoventral patterning on a realistic 3D neural tube and found that key features of neural tube patterning could be recapitulated. Doing so, we demonstrate how data and models from different sources can be combined to simulate complex in vivo processes.

• Author: Max Brambach; Ariane Ernst; Sara Nolbrant; Janelle Drouin-Ouellet; Agnete Kirkeby; Malin Parmar; Victor Olariu
• Department/s: StemTherapy: National Initiative on Stem Cells for Regenerative Therapy; Developmental and Regenerative Neurobiology; MultiPark: Multidisciplinary research focused on Parkinson´s disease; Human Neural Developmental Biology; Computational Biology and Biological Physics - Has been reorganised
• Publishing year: 2021-06-25
• Language: English
• Publication/Series: iScience
• Volume: 24
• Issue: 6
• Links: http://dx.doi.org/10.1016/j.isci.2021.102559
• Document type: Journal article
• Publisher: Elsevier
• Topic: Developmental Biology; Cell and Molecular Biology; Other Physics Topics
• Keywords: biophysics; neurogenetics; systems neuroscience
• Status: Published
• Research group: Developmental and Regenerative Neurobiology; Human Neural Developmental Biology
• ISBN/ISSN/Other: ISSN: 2589-0042