Downregulation of ribosome biogenesis during early forebrain development
- Boston Children's Hospital, United States
Abstract
Forebrain precursor cells are dynamic during early brain development, yet the underlying molecular changes remain elusive. We observed major differences in transcriptional signatures of precursor cells from mouse forebrain at embryonic days E8.5 vs. E10.5 (before vs. after neural tube closure). Genes encoding protein biosynthetic machinery were strongly downregulated at E10.5. This was matched by decreases in ribosome biogenesis and protein synthesis, together with age-related changes in proteomic content of the adjacent fluids. Notably, c-MYC expression and mTOR pathway signaling were also decreased at E10.5, providing a potential driver for the effects on ribosome biogenesis and protein synthesis. Interference with c-MYC at E8.5 prematurely decreased ribosome biogenesis, while persistent c-MYC expression in cortical progenitors increased transcription of protein biosynthetic machinery and enhanced ribosome biogenesis, as well as enhanced progenitor proliferation leading to subsequent macrocephaly. These findings indicate large, coordinated changes in molecular machinery of forebrain precursors during early brain development.
Data availability
Sequencing data have been deposited in GEO under accession number GSE100421.
Article and author information
Author details
Funding
National Science Foundation (Graduate Research Fellowship)
- Kevin F Chau
National Institutes of Health (R01 NS088566)
- Maria K Lehtinen
Pediatric Hydrocephalus Foundation (Research grant)
- Maria K Lehtinen
Simons Foundation (SFARI Pilot Grant)
- Maria K Lehtinen
New York Stem Cell Foundation (Robertson Investigator)
- Maria K Lehtinen
National Institutes of Health (NIH T32 HL110852)
- Kevin F Chau
National Institutes of Health (NIH T32 HL110852)
- Ryann M Fame
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Ethics
Animal experimentation: All animal experimentation was carried out under protocols approved by the IACUC of Boston Children's Hospital (protocol number 17-10-3547R).
Copyright
© 2018, Chau 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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Downregulation of ribosome biogenesis during early forebrain development
eLife 7:e36998.
https://doi.org/10.7554/eLife.36998
