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

Brambach, Max ; Ernst, Ariane ; Nolbrant, Sara LU ; Drouin-Ouellet, Janelle LU ; Kirkeby, Agnete LU ; Parmar, Malin LU orcid and Olariu, Victor LU (2021) In iScience 24(6).
Abstract

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... (More)

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.

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author
; ; ; ; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
biophysics, neurogenetics, systems neuroscience
in
iScience
volume
24
issue
6
article number
102559
pages
16 pages
publisher
Elsevier
external identifiers
  • pmid:34142058
  • scopus:85107155570
ISSN
2589-0042
DOI
10.1016/j.isci.2021.102559
project
Computational Science for Health and Environment
Patterning of the neural tube:​ A 3D computational modelling approach
language
English
LU publication?
yes
id
c7eba300-55f9-4984-90e8-3038cc2e0747
date added to LUP
2021-06-18 13:17:38
date last changed
2025-04-04 15:16:52
@article{c7eba300-55f9-4984-90e8-3038cc2e0747,
  abstract     = {{<p>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.</p>}},
  author       = {{Brambach, Max and Ernst, Ariane and Nolbrant, Sara and Drouin-Ouellet, Janelle and Kirkeby, Agnete and Parmar, Malin and Olariu, Victor}},
  issn         = {{2589-0042}},
  keywords     = {{biophysics; neurogenetics; systems neuroscience}},
  language     = {{eng}},
  month        = {{06}},
  number       = {{6}},
  publisher    = {{Elsevier}},
  series       = {{iScience}},
  title        = {{Neural tube patterning : from a minimal model for rostrocaudal patterning toward an integrated 3D model}},
  url          = {{http://dx.doi.org/10.1016/j.isci.2021.102559}},
  doi          = {{10.1016/j.isci.2021.102559}},
  volume       = {{24}},
  year         = {{2021}},
}