A transposase-derived gene required for human brain development
Vertebrate brain development is associated with prominent neuronal cell death and DNA breaks, but their causes and functions are not well understood. DNA transposable elements could contribute to somatic genome rearrangements; however, their contributions to brain development are largely unknown. PiggyBac transposable element derived 5 (PGBD5) is an evolutionarily conserved vertebrate DNA transposase-derived gene with DNA remodeling activities in human cells. Here, we show that PGBD5 contributes to normal brain development in mice and humans, and its deficiency causes disorder of intellectual disability, movement disorders, and epilepsy. In mice, Pgbd5 is required for the developmental induction of postmitotic DNA breaks and recurrent somatic brain genome rearrangements. In the cerebral cortex, loss of Pgbd5 leads to aberrant neuronal gene expression, including of specific types of glutamatergic neurons, which partly explains the features of PGBD5 deficiency in humans. Thus, PGBD5 is a transposase-derived gene required for brain development in mammals.
Authors
- Carolina I. Galaz-Montoya (ORCID: https://orcid.org/0000-0002-9180-8202)
- Alex Proekt
- Miriam Essid
- Phillip Demarest (ORCID: https://orcid.org/0009-0005-0330-8785)
- Hanène Benrhouma
- Casie Reed (ORCID: https://orcid.org/0000-0001-9012-3183)
- Ichraf Kraoua
- Halil Tuna Akar (ORCID: https://orcid.org/0000-0003-1982-8046)
- Xiaolan Zhao (ORCID: https://orcid.org/0000-0002-8302-6905)
- Caroline Oliveira Nava
- Patricia Cornejo (ORCID: https://orcid.org/0000-0001-5096-6047)
- Helen Mueller
- Huma Arshad Cheema (ORCID: https://orcid.org/0000-0002-0463-687X)
- Meriem Ben Hafsa (ORCID: https://orcid.org/0000-0003-0022-7523)
- Nicholas D. Socci (ORCID: https://orcid.org/0000-0002-8254-6925)
- Miklós Tóth (ORCID: https://orcid.org/0000-0001-5031-4401)
- Alex M. Pagnozzi (ORCID: https://orcid.org/0000-0001-7931-1204)
- Tzippora Chwat-Edelstein
- Elias Rodríguez-Fos (ORCID: https://orcid.org/0000-0002-2555-0178)
- Mercè Planas-Fèlix (ORCID: https://orcid.org/0000-0002-8267-576X)
- Sara A. Lewis (ORCID: https://orcid.org/0000-0003-2560-1681)
- Raul Rabadan
- Matthew Hayes (ORCID: https://orcid.org/0000-0002-0457-8550)
- Peter Bauer
- Ali Dursun
- Claudia L Kleinmann
- Makiko Yamada
- Muhammad Nadeem Anjum
- Anika Nabila
- Paul Bergin
- Yves Bigot
- Henry Houlden
- Rodrigo LÓPEZ GUTIÉRREZ
- Alex Kentsis
- Junfei Zhao
- Luz Jubierre Zapater
- Emilie Bourel-Ponchel
- Reza Maroofian
- R. Köksal Özgül
- Giovanni Zifarelli
- Daniel Cameron
Institutions
- Institució Catalana de Recerca i Estudis Avançats (ES)
- Commonwealth Scientific and Industrial Research Organisation (AU)
- Centre National de la Recherche Scientifique (FR)
- Barrow Neurological Institute (US)
- Memorial Sloan Kettering Cancer Center (US)
- University of Arizona (US)
- Inserm (FR)
- Xavier University of Louisiana (US)
- Cornell University (US)
- Barcelona Supercomputing Center (ES)
- Jewish General Hospital (CA)
- University of Health Sciences Lahore (PK)
- Sorbonne Université (FR)
- Kettering University (US)
- Institut National de Recherche pour l'Agriculture, l'Alimentation et l'Environnement (FR)
- Centre Hospitalier Universitaire Amiens-Picardie (FR)
- Assistance Publique – Hôpitaux de Paris (FR)
- Physiologie de la Reproduction et des Comportements (FR)
- Phoenix Children's Hospital (US)
- Centogene (Germany) (DE)
- Australian e-Health Research Centre (AU)
- National Hospital for Neurology and Neurosurgery (GB)
- National Institute of Neurology Mongi-Ben Hamida (TN)
- University College London (GB)
- Université de Picardie Jules Verne (FR)
- McGill University (CA)
- Tunis El Manar University (TN)
- Hacettepe University (TR)
- Columbia University (US)
- University of Pennsylvania (US)
- Universitat Politècnica de Catalunya (ES)
Publication Details
- Journal
- Science Advances
- Published
- 2026-01-14
- DOI
- https://doi.org/10.1126/sciadv.adv7530
- Citations
- 1
- Primary Topic
- Chromosomal and Genetic Variations
- Type
- article
- Field-Weighted Citation Impact
- 31.34