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Light- and chemical-induced ciliary signaling governs dorsal/ventral regionalization of human telencephalic organoids.

Overview

Authors: Issei S. Shimada1, Akari Goto1, Yutaka Hashimoto1, Hajime Inoue2, Takuto Sugawara2, Tomohiro Doura2, Tsubasa Fujita1, Toshiaki Iwata1, Riko Shimmoto1, Hiroshi Takase3, Masayuki Itoh4, Shigeki Kiyonaka2,5, Yoichi Kato1
ORCID iDs: Issei S. Shimada, Tomohiro Doura, Masayuki Itoh, Shigeki Kiyonaka, Yoichi Kato
  1. Department of Cell Biology, Graduate School of Medical Sciences, Nagoya City University,Nagoya, Aichi Japan
  2. Department of Biomolecular Engineering, Graduate School of Engineering, Nagoya University,Nagoya, Aichi Japan
  3. Core Laboratory, Graduate School of Medical Sciences, Nagoya City University,Nagoya, Aichi Japan
  4. Department of Biochemistry and Cellular Biology, National Center of Neurology and Psychiatry,Kodaira, Tokyo Japan
  5. Research Institute for Quantum and Chemical Innovation, Institutes of Innovation for Future Society, Nagoya University,Nagoya, Aichi Japan
Institutions: Nagoya City University (Japan); Nagoya University (Japan); National Center of Neurology and Psychiatry (Japan)
Journal: Nature communications, volume 17, issue 1, article 6712
Dates: received 14 July 2025; accepted 13 May 2026; published online 22 May 2026
Type: Research article · Language: English
License: CC BY
Identifiers: DOI 10.1038/s41467-026-73505-2 · PMID 42173885 · PMCID PMC13385379 · OpenAlex W7162127142
Open access: gold, a free copy (OpenAlex)
Status: code verified
Categories: human (organism)
Methods: Preprocessing, Statistics, Evoked potentials
Keywords: Neural stem cells, Ciliogenesis, Neural patterning
MeSH: Cilia*, Organoids*, Signal Transduction*, Telencephalon*, ADP-Ribosylation Factors, Cyclic AMP, Hedgehog Proteins, Humans, Neural Stem Cells, Receptors, G-Protein-Coupled (* major topic)
Topic: Genetic and Kidney Cyst Diseases (Genetics, Biochemistry, Genetics and Molecular Biology), according to OpenAlex
Funding: Nagoya City University (2401101); MEXT | NINS | National Institute for Basic Biology (NIBB) (24NIBB460); Japan Society for the Promotion of Science (21K07803, 24K02425, 20K16157, 24H02265, 24H00492, 24K21823, 20K21584); Mochida Memorial Foundation for Medical and Pharmaceutical Research (公益財団法人 持田記念医学薬学振興財団); Takeda Science Foundation; Daiko Foundation, The Hori Science and Arts Foundation, iPS Academia Japan Inc., Leave a Nest Co., Ltd. (Ikeda Rika Award) and the Nitto Foundation; Japan Agency for Medical Research and Development (24zf0127012)
Citations: cited by 1 paper (Europe PMC); 85 references in the paper

Abstract

Neural stem/progenitor cells (NPCs) have primary cilia, which are critical organelles for Sonic hedgehog signaling. However, little is known about the components of primary cilia in NPCs and whether manipulating signaling in the cilia is sufficient to alter dorsal/ventral regional identity. Using a human telencephalic organoid model, we perform comprehensive proteomic profiling of NPC cilia and find enrichment in GTPase signaling. Deletion of the ciliary GTPase ARL13B reduces ciliary localization of GPR161, an orphan G protein-coupled receptor 161 that negatively regulates Sonic hedgehog, resulting in ventralization of NPCs. GPR161 deletion also induces ventralization. To investigate whether manipulation of ciliary signaling is sufficient to restore dorsal identity in this context, we optogenetically elevate ciliary cAMP, rescuing dorsal fate in GPR161 KO organoids. Furthermore, chemogenetic induction of GPR161 removal from cilia is sufficient to increase ventral NPCs. These data indicate that ciliary signaling functions as a critical switch regulating dorsal/ventral fate decisions.

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.

Zenodo 19492078

License: CC-BY-4.0
State: the link answers, verified on 28 September 2026
Evidence: files inventoried
Size: 1 file, 0 scripts
Software Heritage: not checked
Found in: “Code availability”
Not found: README, license file, CITATION.cff, environment file, tests, continuous integration, documentation
Availability: 1 check, the latest on 28 September 2026: the link answers (HTTP 200)
  • 28 September 2026: the link answers (HTTP 200)
At the source:

Code availability

Code for the Arduino Uno gravity-relay module for optogenetics is available at 10.5281/zenodo.19492078.

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

RNA sequencing data have been deposited in the DNA Data Bank of Japan (DDBJ) BioProject (PRJDB20782 [https://ddbj.nig.ac.jp/search/entry/bioproject/PRJDB20782]). Mass spectrometry analysis data have been deposited in the Japan Proteome Standard Repository (JPST003807 [https://repository.jpostdb.org/entry/JPST003807])85. CUT&Tag data ERR10092480 (https://www.ebi.ac.uk/ena/browser/view/ERR10092480) was used for the reanalysis31. Requests for further information and resources should be directed to and will be fulfilled by the lead contact, Dr. Issei S. Shimada. All unique reagents generated in this study are available from the lead contact with a completed materials transfer agreement. Source data are provided with this paper.

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, 28 September 2026: the first record

Recorded: type, language, journal, volume, issue, pages, dates, 13 authors, 3 keywords, 10 MeSH terms, 7 funders, 84 references.

Cite

This paper

Shimada, I. S., Goto, A., Hashimoto, Y., Inoue, H., Sugawara, T., Doura, T., Fujita, T., Iwata, T., Shimmoto, R., Takase, H., Itoh, M., Kiyonaka, S., & Kato, Y. (2026). Light- and chemical-induced ciliary signaling governs dorsal/ventral regionalization of human telencephalic organoids. Nature communications, 17(1), 6712. https://doi.org/10.1038/s41467-026-73505-2

BibTeX

@article{shimada2026light,
author = {Shimada, Issei S. and Goto, Akari and Hashimoto, Yutaka and Inoue, Hajime and Sugawara, Takuto and Doura, Tomohiro and Fujita, Tsubasa and Iwata, Toshiaki and Shimmoto, Riko and Takase, Hiroshi and Itoh, Masayuki and Kiyonaka, Shigeki and Kato, Yoichi},
title = {{Light- and chemical-induced ciliary signaling governs dorsal/ventral regionalization of human telencephalic organoids}},
journal = {Nature communications},
year = {2026},
month = may,
volume = {17},
number = {1},
pages = {6712},
publisher = {Nature Publishing Group},
issn = {2041-1723},
doi = {10.1038/s41467-026-73505-2},
url = {https://doi.org/10.1038/s41467-026-73505-2},
pmid = {42173885},
pmcid = {PMC13385379}
}

RIS

TY - JOUR
AU - Shimada, Issei S.
AU - Goto, Akari
AU - Hashimoto, Yutaka
AU - Inoue, Hajime
AU - Sugawara, Takuto
AU - Doura, Tomohiro
AU - Fujita, Tsubasa
AU - Iwata, Toshiaki
AU - Shimmoto, Riko
AU - Takase, Hiroshi
AU - Itoh, Masayuki
AU - Kiyonaka, Shigeki
AU - Kato, Yoichi
TI - Light- and chemical-induced ciliary signaling governs dorsal/ventral regionalization of human telencephalic organoids
T2 - Nature communications
J2 - Nat Commun
PY - 2026
DA - 2026/05/22
VL - 17
IS - 1
SP - 6712
SN - 2041-1723
PB - Nature Publishing Group
DO - 10.1038/s41467-026-73505-2
UR - https://doi.org/10.1038/s41467-026-73505-2
LA - en
ER -

CSL-JSON

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