Conserved sleep disturbances in FOXP1 syndrome originate from developmental dysregulation of peptidergic signaling
Mireia Coll-Tané, Ilse Eidhof, Jie Han, Nicholas Raun, Lara V. van Renssen, Simon E. Fisher, Matthew S. Kayser, Tjitske Kleefstra, Sigrid Pillen, Caitlin M. Hudac, Jordi Mayneris-Perxachs, Marieke Klein, Saskia Koene, Anna Castells-Nobau, Annette Schenck
Mireia Coll-Tané, Ilse Eidhof, Jie Han, Nicholas Raun, Lara V. van Renssen, Simon E. Fisher, Matthew S. Kayser, Tjitske Kleefstra, Sigrid Pillen, Caitlin M. Hudac, Jordi Mayneris-Perxachs, Marieke Klein, Saskia Koene, Anna Castells-Nobau, Annette Schenck
View: Text | PDF
Research Article Clinical Research Neuroscience

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

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.

Authors

Mireia Coll-Tané, Ilse Eidhof, Jie Han, Nicholas Raun, Lara V. van Renssen, Simon E. Fisher, Matthew S. Kayser, Tjitske Kleefstra, Sigrid Pillen, Caitlin M. Hudac, Jordi Mayneris-Perxachs, Marieke Klein, Saskia Koene, Anna Castells-Nobau, Annette Schenck

×
Problems with a PDF?

This file is in Adobe Acrobat (PDF) format. If you have not installed and configured the Adobe Acrobat Reader on your system.

Having trouble reading a PDF?

PDFs are designed to be printed out and read, but if you prefer to read them online, you may find it easier if you increase the view size to 125%.

Having trouble saving a PDF?

Many versions of the free Acrobat Reader do not allow Save. You must instead save the PDF from the JCI Online page you downloaded it from. PC users: Right-click on the Download link and choose the option that says something like "Save Link As...". Mac users should hold the mouse button down on the link to get these same options.

Having trouble printing a PDF?

  1. Try printing one page at a time or to a newer printer.
  2. Try saving the file to disk before printing rather than opening it "on the fly." This requires that you configure your browser to "Save" rather than "Launch Application" for the file type "application/pdf", and can usually be done in the "Helper Applications" options.
  3. Make sure you are using the latest version of Adobe's Acrobat Reader.

Supplemental data - Download (2.15 MB)

Advertisement