SAFB regulates hippocampal stem cell fate by targeting Drosha to destabilize Nfib mRNA
- University of Basel, Switzerland
Abstract
Neural stem cells (NSCs) are multipotent and correct fate determination is crucial to guarantee brain formation and homeostasis. How NSCs are instructed to generate neuronal or glial progeny is not well understood. Here we addressed how murine adult hippocampal NSC fate is regulated and describe how Scaffold Attachment Factor B (SAFB) blocks oligodendrocyte production to enable neuron generation. We found that SAFB prevents NSC expression of the transcription factor Nuclear Factor I/B (NFIB) by binding to sequences in the Nfib mRNA and enhancing Drosha-dependent cleavage of the transcripts. We show that increasing SAFB expression prevents oligodendrocyte production by multipotent adult NSCs, and conditional deletion of Safb increases NFIB expression and oligodendrocyte formation in the adult hippocampus. Our results provide novel insights into a mechanism that controls Drosha functions for selective regulation of NSC fate by modulating the post-transcriptional destabilization of Nfib mRNA in a lineage-specific manner.
Data availability
Proteomics mass spectrometry data have been deposited in PRIDE:Project accession: PXD017677Project DOI: 10.6019/PXD017677
Article and author information
Author details
Funding
Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung (31003A_162609)
- Verdon Taylor
Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung (31003A_182388)
- Verdon Taylor
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Ethics
Animal experimentation: According to Swiss Federal and Swiss Veterinary office regulations, all mice were bred and kept in a specific pathogen-free animal facility with 12 hours day-night cycle and free access to clean food and water. All mice were healthy and immunocompetent. All procedures were approved by the Basel Cantonal Veterinary Office under license number 2537 (Ethics commission Basel-Stadt, Basel Switzerland).
Copyright
© 2024, Forcella et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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SAFB regulates hippocampal stem cell fate by targeting Drosha to destabilize Nfib mRNA
eLife 13:e74940.
https://doi.org/10.7554/eLife.74940
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