Abstract
SummaryRostrocaudal 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.
Highlights
In Parkinson’s disease (PD), the dopaminergic neurons (DA) of the substantia nigra of the brain undergo pathological deterioration
We present a minimal gene regulatory model for rostrocaudal patterning, whose tristable topology was determined in a data-driven way
We identified the repression of hindbrain fate as promising strategy for the improvement of current protocols for the generation of dopaminergic neurons
Summary
In Parkinson’s disease (PD), the dopaminergic neurons (DA) of the substantia nigra of the brain undergo pathological deterioration. Various protocols have been developed to efficiently derive DA progenitors from human embryonic stem cells; many of them focusing on tuning a combination of WNT, SHH and FGF8 with great success (Adil et al, 2017; Cho et al, 2008; Gonzalez et al, 2013; Kim et al, 2002; Kirkeby et al, 2012; Nolbrant et al, 2017). These protocols are inspired by the mechanisms and actors found in the development of the neural tube in vivo. A better understanding of correct and reliable DA differentiation in vivo would shed light on the development of the early brain, and contribute to improving current in vitro protocols for midbrain DA neuron generation
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
