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Heterogeneity of Sonic Hedgehog response dynamics and fate specification in single neural progenitors.

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LICENSE at commit 29286e8, under CC-BY-4.0 · at the source

Overview

Authors: Fengzhu Xiong1,2, Andrea R Tentner1, Sandy Nandagopal1, Tom W Hiscock1,3, Peng Huang4, Sean G Tsung-Megason1
ORCID iDs: Fengzhu Xiong, Andrea R Tentner, Tom W Hiscock, Peng Huang, Sean G Tsung-Megason
  1. Department of Systems Biology, Harvard Medical School Boston United States
  2. Gurdon Institute and Department of Physiology, Development and Neuroscience, University of Cambridge Cambridge United Kingdom
  3. Institute of Medical Sciences, School of Medicine, Medical Sciences and Nutrition, University of Aberdeen Aberdeen United Kingdom
  4. Department of Biochemistry and Molecular Biology, University of Calgary Calgary Canada
Institutions: Harvard University (United States); University of Cambridge (United Kingdom); University of Aberdeen (United Kingdom); University of Calgary (Canada)
Journal: eLife, volume 13, article RP96980
Dates: published online 15 April 2026
Type: Research article · Language: English
License: CC BY
Identifiers: DOI 10.7554/elife.96980 · PMID 41984520 · PMCID PMC13082785 · OpenAlex W4399139414
Open access: gold, a free copy (OpenAlex)
Status: code verified
Categories: zebrafish (organism), developmental (subfield)
Methods: Machine learning, Evoked potentials
Keywords: neural tube, morphogen, cell fate, single-cell tracking, heterogeneity, Zebrafish
MeSH: Hedgehog Proteins*, Neural Stem Cells*, Zebrafish*, Zebrafish Proteins*, Animals, Cell Differentiation, Gene Expression Regulation, Developmental, Motor Neurons, Neural Tube, Signal Transduction (* major topic)
Journal subjects: Developmental Biology
Topic: Hedgehog Signaling Pathway Studies (Molecular Biology, Biochemistry, Genetics and Molecular Biology), according to OpenAlex
Funding: National Institutes of Health (GM107733); Engineering and Physical Sciences Research Council (EP/X023761/1)
Citations: cited by 2 papers (Europe PMC); 34 references in the paper

Abstract

During neural tube patterning, a gradient of Sonic hedgehog (Shh) signaling specifies ventral progenitor fates. The cellular response to Shh is processed through a genetic regulatory network (GRN) to specify distinct fate decisions. This process integrates Shh response level, duration, and other inputs and is affected by noise in signaling and cell position. How reliably the Shh response profile predicts the fate choice of a single cell remains unclear. Here, we use live imaging to track neural progenitors in developing zebrafish and quantify both Shh and fate reporters in single cells over time. We found that there is significant heterogeneity between Shh response and fate choice in single cells. We quantitatively modeled reporter intensities to obtain single-cell response levels over time and systematically evaluated their correlation with cell fate specification. Motor neuron progenitors (pMNs) exhibit a high degree of variability in their Shh responses, which is particularly prominent in the posterior neural tube where the Shh response dynamics are similar to those of the more ventrally fated lateral floor plate cells (LFPs). Our results highlight the precision limit of morphogen-interpretation GRNs in small and dynamic target cell fields.

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

Repository

Its files are read in the Code ↔ Paper reader above.

xionglab/NT_heterogeneity

License: CC-BY-4.0
State: the link answers, verified on 29 September 2026
Evidence: files inventoried
Commit: 29286e8ea6689beb34dfe5b60d77a8dc9ce8f65d, 9 April 2026
Size: 3 files
Software Heritage: not archived
Found in: “Data availability”
Holds: README, license file
Not found: CITATION.cff, environment file, tests, continuous integration, documentation
Availability: 1 check, the latest on 29 September 2026: the link answers
  • 29 September 2026: the link answers
2 files
At the source: github.com/xionglab/NT_heterogeneity

The paper's code and data availability statement is in the Data section.

Tracing map

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Data

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Data availability

Full analysis protocols, scripts and sample datasets are available for download here: https://github.com/xionglab/NT_heterogeneity (copy archived at Xiong, 2024).

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

Versions

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Version 1, 29 September 2026: the first record

Recorded: type, language, journal, volume, pages, dates, 6 authors, 6 keywords, 10 MeSH terms, 2 funders, 33 references.

Cite

This paper

Xiong, F., Tentner, A. R., Nandagopal, S., Hiscock, T. W., Huang, P., & Tsung-Megason, S. G. (2026). Heterogeneity of Sonic Hedgehog response dynamics and fate specification in single neural progenitors. eLife, 13, RP96980. https://doi.org/10.7554/elife.96980

BibTeX

@article{xiong2026heterogeneity,
author = {Xiong, Fengzhu and Tentner, Andrea R and Nandagopal, Sandy and Hiscock, Tom W and Huang, Peng and Tsung-Megason, Sean G},
title = {{Heterogeneity of Sonic Hedgehog response dynamics and fate specification in single neural progenitors}},
journal = {eLife},
year = {2026},
month = apr,
volume = {13},
pages = {RP96980},
publisher = {eLife Sciences Publications, Ltd},
issn = {2050-084X},
doi = {10.7554/elife.96980},
url = {https://doi.org/10.7554/elife.96980},
pmid = {41984520},
pmcid = {PMC13082785}
}

RIS

TY - JOUR
AU - Xiong, Fengzhu
AU - Tentner, Andrea R
AU - Nandagopal, Sandy
AU - Hiscock, Tom W
AU - Huang, Peng
AU - Tsung-Megason, Sean G
TI - Heterogeneity of Sonic Hedgehog response dynamics and fate specification in single neural progenitors
T2 - eLife
J2 - eLife
PY - 2026
DA - 2026/04/15
VL - 13
SP - RP96980
SN - 2050-084X
PB - eLife Sciences Publications, Ltd
DO - 10.7554/elife.96980
UR - https://doi.org/10.7554/elife.96980
LA - en
ER -

CSL-JSON

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"id": "10.7554/elife.96980",
"type": "article-journal",
"title": "Heterogeneity of Sonic Hedgehog response dynamics and fate specification in single neural progenitors",
"container-title": "eLife",
"author": [
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"family": "Xiong",
"given": "Fengzhu"
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{
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"given": "Andrea R"
},
{
"family": "Nandagopal",
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{
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"container-title-short": "eLife",
"volume": "13",
"page": "RP96980",
"DOI": "10.7554/elife.96980",
"PMID": "41984520",
"PMCID": "PMC13082785",
"ISSN": "2050-084X",
"publisher": "eLife Sciences Publications, Ltd",
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"language": "en",
"issued": {
"date-parts": [
[
2026,
4,
15
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]
}
}

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