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Combining in vitro and in silico approaches to model neural tube patterning and isthmic organizer formation.

Overview

Authors: Fredrik Bertilsson1, Alexander Degener1, Paulina Ibek1,2, Gaurav Singh Rathore3, Emil Andersson1, Pedro Rifes3, Agnete Kirkeby3,4,5, Victor Olariu1
ORCID iDs: Agnete Kirkeby
  1. Computational Science for Health and Environment, Department of Earth and Environmental Sciences, Lund University,Lund, Sweden
  2. Department of Experimental Medical Science, Lund University,Lund, Sweden
  3. Department of Neuroscience, University of Copenhagen,Copenhagen, Denmark
  4. Developmental and Regenerative Neurobiology, Department of Experimental Medical Science, Lund University,Lund, Sweden
  5. Wallenberg Neuroscience Center and Lund Stem Cell Center, Lund University,Lund, Sweden
Institutions: Lund University (Sweden); University of Copenhagen (Denmark)
Journal: NPJ systems biology and applications, volume 12, issue 1, article 126
Dates: received 23 April 2026; accepted 8 August 2026; published online 21 August 2026
Type: Research article · Language: English
License: CC BY
Identifiers: DOI 10.1038/s41540-026-00813-0 · PMID 42629366 · PMCID PMC13498569 · OpenAlex W7203891591
Open access: gold, a free copy (OpenAlex)
Status: dead link
Categories: human (organism), developmental (subfield)
Methods: Smoothing, state filtering, decompositions, Machine learning, Connectivity
Keywords: Computational biology and bioinformatics, Developmental biology, Neuroscience, Systems biology
MeSH: Body Patterning*, Neural Tube*, Organizers, Embryonic*, Animals, Computer Simulation, Embryonic Development, Gene Expression Regulation, Developmental, Humans, Models, Biological (* major topic)
Topic: Single-cell and spatial transcriptomics (Molecular Biology, Biochemistry, Genetics and Molecular Biology), according to OpenAlex
Funding: Knut and Alice Wallenberg Foundation to SciLifeLab for research in Data-driven Life Science and Wallenberg AI Autonomous Systems and Software Program (DDLS-WASP); Crafoord Foundation; Novo Nordisk Foundation Center for Basic Metabolic Research; Lundbeck Foundation; Innovation Fund Denmark; EC | EU Framework Programme for Research and Innovation H2020 | H2020 Priority Excellent Science | H2020 European Research Council (H2020 Excellent Science - European Research Council)
Citations: not cited yet (Europe PMC); 53 references in the paper
Research resources: RRID:CVCL_9773

Abstract

During early embryonic development, the human neural tube is formed and patterned through spatial regionalization of cell identity, driven by gene regulatory responses to morphogen gradients. However, many of the underlying mechanisms remain unclear. Here, we integrate single-cell RNA sequencing data from in vitro emulation of neural tube patterning to develop computational models of rostral-caudal and dorsal-ventral patterning. By embedding these models in a 3D geometry, we reveal how transient morphogen signals induce irreversible patterns consistent with developmental biology and experimental data. Notably, our framework accurately captures the formation and maintenance of the isthmic organizer at the mid-hindbrain boundary, providing a realistic and mechanistic picture of neural tube patterning. This integrated approach bridges in vitro experimentation and computational modeling to uncover fundamental principles of neural development.

Reproduced under the paper's license (CC BY), from the paper cited above.

Code

No file of the authors' code could be read here: it is described below, and read at its source.

codebyad/model_neural_tube_patterning_and_isthmic_organizer_formation

License: none: the authors keep all their rights
State: the link is dead, verified on 27 September 2026
Evidence: found in the paper
Software Heritage: not archived
Found in: “Code availability”
Not found: README, license file, CITATION.cff, environment file, tests, continuous integration, documentation
Availability: 1 check, the latest on 27 September 2026: the link is dead
  • 27 September 2026: the link is dead
At the source: github.com/CodeByAD/Model_Neural_Tube_Patterning_and_Isthmic_Organizer_Formation/tree/main

Code availability

The custom computer code, scripts, and simulation workflows developed and used in this study to model neural tube patterning and isthmic organizer formation are publicly available on GitHub at https://github.com/CodeByAD/Model_Neural_Tube_Patterning_and_Isthmic_Organizer_Formation/tree/main.

Reproduced under the paper's license (CC BY), from the paper cited above.

Tracing map

Proposed by the machine: these links were found in the paper and verified at the source, without human review. The map will receive a Zenodo DOI once one of the paper's authors has validated it with their ORCID.

What the map holds:

  • 1 repository of the authors' code, each at its verified commit, with its license and how the link was found in the paper;
  • 0 scripts, each with its path and the digest of its content;
  • no match between paragraphs and code yet;
  • neither the text of the paper nor the code itself.

Its JSON (tracing-map.json) is deposited on Zenodo with its DOI once the map is validated.

Data

No dataset and no data link were found in the paper.

Data availability

Processed MiSTR single-cell and single-nucleus transcriptomic datasets from Rathore et al. are publicly available through the UCSC Cell Browser at https://cells.ucsc.edu/?ds=neural-tube-organoids11. In the present study, this resource is relevant to the MiSTR scRNA-seq data used to generate time-resolved expression inputs for model fitting and comparison, specifically the R/C dorsal and R/C ventral MiSTR datasets from days 0, 1, 2, 5, 9, and 14.

Reproduced under the paper's license (CC BY), from the paper cited above.

Versions

The history of this record: each version stored by the harvester or made by a correction of its authors or of the maintainers of its code, and what changed in its facts. The texts of the paper (its abstract, its availability statements) are not part of it; versions that changed only those are not listed.

Version 1, 27 September 2026: the first record

Recorded: type, language, journal, volume, issue, pages, dates, 8 authors, 4 keywords, 9 MeSH terms, 6 funders, 51 references, 1 RRID.

Cite

This paper

Bertilsson, F., Degener, A., Ibek, P., Rathore, G. S., Andersson, E., Rifes, P., Kirkeby, A., & Olariu, V. (2026). Combining in vitro and in silico approaches to model neural tube patterning and isthmic organizer formation. NPJ systems biology and applications, 12(1), 126. https://doi.org/10.1038/s41540-026-00813-0

BibTeX

@article{bertilsson2026combining,
author = {Bertilsson, Fredrik and Degener, Alexander and Ibek, Paulina and Rathore, Gaurav Singh and Andersson, Emil and Rifes, Pedro and Kirkeby, Agnete and Olariu, Victor},
title = {{Combining in vitro and in silico approaches to model neural tube patterning and isthmic organizer formation}},
journal = {NPJ systems biology and applications},
year = {2026},
month = aug,
volume = {12},
number = {1},
pages = {126},
publisher = {Nature Publishing Group},
issn = {2056-7189},
doi = {10.1038/s41540-026-00813-0},
url = {https://doi.org/10.1038/s41540-026-00813-0},
pmid = {42629366},
pmcid = {PMC13498569}
}

RIS

TY - JOUR
AU - Bertilsson, Fredrik
AU - Degener, Alexander
AU - Ibek, Paulina
AU - Rathore, Gaurav Singh
AU - Andersson, Emil
AU - Rifes, Pedro
AU - Kirkeby, Agnete
AU - Olariu, Victor
TI - Combining in vitro and in silico approaches to model neural tube patterning and isthmic organizer formation
T2 - NPJ systems biology and applications
J2 - NPJ Syst Biol Appl
PY - 2026
DA - 2026/08/21
VL - 12
IS - 1
SP - 126
SN - 2056-7189
PB - Nature Publishing Group
DO - 10.1038/s41540-026-00813-0
UR - https://doi.org/10.1038/s41540-026-00813-0
LA - en
ER -

CSL-JSON

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