Developmental signals control chromosome segregation fidelity during pluripotency and neurogenesis by modulating replicative stress.


Journal

Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555

Informations de publication

Date de publication:
28 Aug 2024
Historique:
received: 10 11 2023
accepted: 09 08 2024
medline: 28 8 2024
pubmed: 28 8 2024
entrez: 27 8 2024
Statut: epublish

Résumé

Human development relies on the correct replication, maintenance and segregation of our genetic blueprints. How these processes are monitored across embryonic lineages, and why genomic mosaicism varies during development remain unknown. Using pluripotent stem cells, we identify that several patterning signals-including WNT, BMP, and FGF-converge into the modulation of DNA replication stress and damage during S-phase, which in turn controls chromosome segregation fidelity in mitosis. We show that the WNT and BMP signals protect from excessive origin firing, DNA damage and chromosome missegregation derived from stalled forks in pluripotency. Cell signalling control of chromosome segregation declines during lineage specification into the three germ layers, but re-emerges in neural progenitors. In particular, we find that the neurogenic factor FGF2 induces DNA replication stress-mediated chromosome missegregation during the onset of neurogenesis, which could provide a rationale for the elevated chromosomal mosaicism of the developing brain. Our results highlight roles for morphogens and cellular identity in genome maintenance that contribute to somatic mosaicism during mammalian development.

Identifiants

pubmed: 39191776
doi: 10.1038/s41467-024-51821-9
pii: 10.1038/s41467-024-51821-9
doi:

Substances chimiques

Bone Morphogenetic Proteins 0
Fibroblast Growth Factor 2 103107-01-3

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

7404

Informations de copyright

© 2024. The Author(s).

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https://creativecommons.org/licenses/by-nc-nd/4.0/deed.en . Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International license.

Auteurs

Anchel de Jaime-Soguero (A)

Centre for Organismal Studies (COS), Heidelberg University, Heidelberg, Germany.

Janina Hattemer (J)

Centre for Organismal Studies (COS), Heidelberg University, Heidelberg, Germany.

Anja Bufe (A)

Centre for Organismal Studies (COS), Heidelberg University, Heidelberg, Germany.

Alexander Haas (A)

Department of Molecular Oncology, Section for Cellular Oncology, University Medical Center Göttingen (UMG), Göttingen, Germany.

Jeroen van den Berg (J)

Oncode Institute, Utrecht, The Netherlands.
Hubrecht Institute, Utrecht, The Netherlands.
KNAW (Royal Netherlands Academy of Arts and Sciences), Utrecht, The Netherlands.
University Medical Center Utrecht, Utrecht, The Netherlands.

Vincent van Batenburg (V)

Oncode Institute, Utrecht, The Netherlands.
Hubrecht Institute, Utrecht, The Netherlands.
KNAW (Royal Netherlands Academy of Arts and Sciences), Utrecht, The Netherlands.
University Medical Center Utrecht, Utrecht, The Netherlands.

Biswajit Das (B)

Department of Medical Biochemistry and Biophysics, Umeå University, Umeå, Sweden.

Barbara di Marco (B)

Department of Clinical Neurobiology, University Hospital Heidelberg and German Cancer Research Center (DKFZ), Heidelberg, Germany.

Stefania Androulaki (S)

Centre for Organismal Studies (COS), Heidelberg University, Heidelberg, Germany.

Nicolas Böhly (N)

Department of Molecular Oncology, Section for Cellular Oncology, University Medical Center Göttingen (UMG), Göttingen, Germany.

Jonathan J M Landry (JJM)

Genomics Core Facility, European Molecular Biology Laboratory (EMBL), Heidelberg, Germany.

Brigitte Schoell (B)

Institute of Human Genetics, Heidelberg University, Heidelberg, Germany.

Viviane S Rosa (VS)

MRC Laboratory of Molecular Biology, Cambridge, UK.

Laura Villacorta (L)

Genomics Core Facility, European Molecular Biology Laboratory (EMBL), Heidelberg, Germany.

Yagmur Baskan (Y)

Centre for Organismal Studies (COS), Heidelberg University, Heidelberg, Germany.

Marleen Trapp (M)

Schaller Research Group, German Cancer Research Center (DKFZ), Heidelberg, Germany.

Vladimir Benes (V)

Genomics Core Facility, European Molecular Biology Laboratory (EMBL), Heidelberg, Germany.

Andrei Chabes (A)

Department of Medical Biochemistry and Biophysics, Umeå University, Umeå, Sweden.

Marta Shahbazi (M)

MRC Laboratory of Molecular Biology, Cambridge, UK.

Anna Jauch (A)

Institute of Human Genetics, Heidelberg University, Heidelberg, Germany.

Ulrike Engel (U)

Nikon Imaging Center at the University of Heidelberg, Bioquant, Heidelberg, Germany.

Annarita Patrizi (A)

Schaller Research Group, German Cancer Research Center (DKFZ), Heidelberg, Germany.

Rocio Sotillo (R)

Division of Molecular Thoracic Oncology, German Cancer Research Center (DKFZ), Heidelberg, Germany.

Alexander van Oudenaarden (A)

Oncode Institute, Utrecht, The Netherlands.
Hubrecht Institute, Utrecht, The Netherlands.
KNAW (Royal Netherlands Academy of Arts and Sciences), Utrecht, The Netherlands.
University Medical Center Utrecht, Utrecht, The Netherlands.

Josephine Bageritz (J)

Centre for Organismal Studies (COS), Heidelberg University, Heidelberg, Germany.

Julieta Alfonso (J)

Department of Clinical Neurobiology, University Hospital Heidelberg and German Cancer Research Center (DKFZ), Heidelberg, Germany.

Holger Bastians (H)

Department of Molecular Oncology, Section for Cellular Oncology, University Medical Center Göttingen (UMG), Göttingen, Germany.

Sergio P Acebrón (SP)

Centre for Organismal Studies (COS), Heidelberg University, Heidelberg, Germany. sergio.acebron@cos.uni-heidelberg.de.

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