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Conserved sleep disturbances in FOXP1 syndrome originate from developmental dysregulation of peptidergic signaling.

Overview

Authors: Mireia Coll-Tané1,2, Ilse Eidhof1,2, Jie Han1,2, Nicholas Raun1,2, Lara V van Renssen1,2, Simon E Fisher3,4, Matthew S Kayser5, Tjitske Kleefstra1,6,7, Sigrid Pillen8, Caitlin M Hudac9,10, Jordi Mayneris-Perxachs11,12, Marieke Klein2,13, Saskia Koene1, Anna Castells-Nobau1,2,11,12, Annette Schenck1,2
ORCID iDs: Nicholas Raun, Simon E Fisher, Jordi Mayneris-Perxachs
13 affiliations
  1. Department of Human Genetics and
  2. Donders Institute for Brain, Cognition, and Behaviour, Radboud University Medical Center, Nijmegen, Netherlands
  3. Language and Genetics Department, Max Planck Institute for Psycholinguistics, Nijmegen, Netherlands
  4. Donders Centre for Neuroscience, Donders Institute for Brain, Cognition, and Behaviour, Radboud University, Nijmegen, Netherlands
  5. Departments of Psychiatry and Neuroscience, Chronobiology and Sleep Institute, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania, USA
  6. Department of Clinical Genetics, Erasmus University Rotterdam, Rotterdam, Netherlands
  7. Center of Excellence for Neuropsychiatry, Vincent van Gogh Institute for Psychiatry, Venray, Netherlands
  8. Kinderslaapexpert BV (Pediatric Sleep Expert Ltd.), Mook, Netherlands
  9. Department of Psychology and
  10. Carolina Autism and Neurodevelopment Research Center, University of South Carolina, Columbia, South Carolina, USA
  11. Nutrition, Eumetabolism and Health Group and Integrative Systems Medicine and Biology Group, Girona Biomedical Research Institute (IDIBGI-CERCA), Girona, Spain
  12. Centro de Investigación Biomédica en Red de Fisiopatología de la Obesidad y Nutrición (CIBEROBN), Madrid, Spain
  13. Department of Medical Neuroscience, Radboud University Medical Center, Nijmegen, Netherlands
Institutions: Radboud University Nijmegen (Netherlands); Radboud University Medical Center (Netherlands); Donders Institute for Brain, Cognition and Behaviour (Netherlands); Max Planck Institute for Psycholinguistics (Netherlands); Donders Centre for Neuroscience (Netherlands); University of Pennsylvania (United States); Erasmus University Rotterdam (Netherlands); University of South Carolina (United States); Spanish Biomedical Research Centre in Physiopathology of Obesity and Nutrition (Spain); Institut d'Investigació Biomèdica de Girona (Spain)
Journal: The Journal of clinical investigation, volume 136, issue 7, article e193475
Dates: received 17 March 2025; accepted 3 February 2026; published online 1 April 2026
Type: Research article · Language: English
License: CC BY
Identifiers: DOI 10.1172/jci193475 · PMID 41919501 · PMCID PMC13038207 · OpenAlex W7147596286
Open access: gold, a free copy (OpenAlex)
Status: data only
Categories: human (organism), drosophila (organism), sleep disorders (population)
Methods: Statistics
Keywords: Clinical Research, Neuroscience, Behavior, Complex traits, Genetic diseases
MeSH: Drosophila Proteins*, Forkhead Transcription Factors*, Neuropeptides*, Repressor Proteins*, Signal Transduction*, Sleep Wake Disorders*, Animals, Drosophila melanogaster, Female, Humans, Male, Neurons, Syndrome (* major topic)
Topic: Sleep and Wakefulness Research (Cognitive Neuroscience, Neuroscience), according to OpenAlex
Funding: Netherlands Organisation for Scientific Research (NWO) ZonMw Veni (09150162010073); Max Planck Society (n/a); ZonMw (09150162010073, 09150181910022, 91718310); Netherlands Organisation for Scientific Research (NWO) ZonMw Vici (09150181910022); Instituto de Salud Carlos III (Madrid, Spain) through the Miguel Servet Program, co-funded by the European Union under the European Social Fund ‘Investing in your future’ (CP24/00033); travelling fellowship by The Company of Biologists (DMMTF1908278); Netherlands Organisation for Scientific Research (NWO) ZonMw Vidi (91718310); Radboudumc junior researcher fellowship (n/a); Radboudumc personal PhD fellowship (n/a)
Citations: not cited yet (Europe PMC); 80 references in the paper

Abstract

Sleep disturbances are among the most prevalent clinical features of FOXP1 syndrome, yet their nature and underlying mechanisms remain unclear. Here, we report that individuals with FOXP1 syndrome suffer from insomnia with sleep maintenance problems and early waking. Consistently, common variants in FOXP genes were associated with insomnia symptoms and short sleep. These sleep disturbances were recapitulated in Drosophila FoxP mutants, which exhibit severely fragmented and reduced sleep. FoxP loss also led to circadian arrhythmicity and impaired the plasticity of neuropeptide pigment dispersing factor–secreting (PDF-secreting) neurons in a non-cell-autonomous manner. FoxP was required during development for adult sleep integrity, particularly in peptidergic neurons. Transcriptomic analyses revealed a dysregulation of genes involved in peptidergic signaling, including hugin. FoxP was expressed in hugin+ neurons (afferent to PDF-secreting neurons) during development, and its knockdown in these cells was sufficient to induce sleep fragmentation. Our findings establish an evolutionarily conserved role for FOXP proteins in the peptidergic regulation of sleep.

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

Code

The paper links to its data, not to its authors' code: see the Data section.

Tracing map

A tracing map links a paper to the code its authors published: this paper has none, so it has no map.

Data

Datasets cited

Data availability

Gene expression data are available in the Gene Expression Omnibus with the accession number GSE293784 (https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE293784). The values for all data points in the graphs are reported in the Supporting Data Values file.

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 2, 28 September 2026

  • Authors: added Jordi Mayneris-Perxachs (0000-0003-3788-3815); removed Jordi Mayneris-Perxachs

Version 1, 28 September 2026: the first record

Recorded: type, language, journal, volume, issue, pages, dates, 15 authors, 5 keywords, 13 MeSH terms, 9 funders, 79 references.

Cite

This paper

Coll-Tané, M., Eidhof, I., Han, J., Raun, N., van Renssen, L. V., Fisher, S. E., Kayser, M. S., Kleefstra, T., Pillen, S., Hudac, C. M., Mayneris-Perxachs, J., Klein, M., Koene, S., Castells-Nobau, A., & Schenck, A. (2026). Conserved sleep disturbances in FOXP1 syndrome originate from developmental dysregulation of peptidergic signaling. The Journal of clinical investigation, 136(7), e193475. https://doi.org/10.1172/jci193475

BibTeX

@article{colltane2026conserved,
author = {Coll-Tané, Mireia and Eidhof, Ilse and Han, Jie and Raun, Nicholas and van Renssen, Lara V and Fisher, Simon E and Kayser, Matthew S and Kleefstra, Tjitske and Pillen, Sigrid and Hudac, Caitlin M and Mayneris-Perxachs, Jordi and Klein, Marieke and Koene, Saskia and Castells-Nobau, Anna and Schenck, Annette},
title = {{Conserved sleep disturbances in FOXP1 syndrome originate from developmental dysregulation of peptidergic signaling}},
journal = {The Journal of clinical investigation},
year = {2026},
month = apr,
volume = {136},
number = {7},
pages = {e193475},
publisher = {American Society for Clinical Investigation},
issn = {0021-9738},
doi = {10.1172/jci193475},
url = {https://doi.org/10.1172/jci193475},
pmid = {41919501},
pmcid = {PMC13038207}
}

RIS

TY - JOUR
AU - Coll-Tané, Mireia
AU - Eidhof, Ilse
AU - Han, Jie
AU - Raun, Nicholas
AU - van Renssen, Lara V
AU - Fisher, Simon E
AU - Kayser, Matthew S
AU - Kleefstra, Tjitske
AU - Pillen, Sigrid
AU - Hudac, Caitlin M
AU - Mayneris-Perxachs, Jordi
AU - Klein, Marieke
AU - Koene, Saskia
AU - Castells-Nobau, Anna
AU - Schenck, Annette
TI - Conserved sleep disturbances in FOXP1 syndrome originate from developmental dysregulation of peptidergic signaling
T2 - The Journal of clinical investigation
J2 - J Clin Invest
PY - 2026
DA - 2026/04/01
VL - 136
IS - 7
SP - e193475
SN - 0021-9738
PB - American Society for Clinical Investigation
DO - 10.1172/jci193475
UR - https://doi.org/10.1172/jci193475
LA - en
ER -

CSL-JSON

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