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Downregulation of ribosome biogenesis during early forebrain development
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). Gene...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
eLife Sciences Publications, Ltd
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5984036/ https://www.ncbi.nlm.nih.gov/pubmed/29745900 http://dx.doi.org/10.7554/eLife.36998 |
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author | Chau, Kevin F Shannon, Morgan L Fame, Ryann M Fonseca, Erin Mullan, Hillary Johnson, Matthew B Sendamarai, Anoop K Springel, Mark W Laurent, Benoit Lehtinen, Maria K |
author_facet | Chau, Kevin F Shannon, Morgan L Fame, Ryann M Fonseca, Erin Mullan, Hillary Johnson, Matthew B Sendamarai, Anoop K Springel, Mark W Laurent, Benoit Lehtinen, Maria K |
author_sort | Chau, Kevin F |
collection | PubMed |
description | 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 potential drivers 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. |
format | Online Article Text |
id | pubmed-5984036 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | eLife Sciences Publications, Ltd |
record_format | MEDLINE/PubMed |
spelling | pubmed-59840362018-06-04 Downregulation of ribosome biogenesis during early forebrain development Chau, Kevin F Shannon, Morgan L Fame, Ryann M Fonseca, Erin Mullan, Hillary Johnson, Matthew B Sendamarai, Anoop K Springel, Mark W Laurent, Benoit Lehtinen, Maria K eLife Neuroscience 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 potential drivers 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. eLife Sciences Publications, Ltd 2018-05-10 /pmc/articles/PMC5984036/ /pubmed/29745900 http://dx.doi.org/10.7554/eLife.36998 Text en © 2018, Chau et al http://creativecommons.org/licenses/by/4.0/ http://creativecommons.org/licenses/by/4.0/This article is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use and redistribution provided that the original author and source are credited. |
spellingShingle | Neuroscience Chau, Kevin F Shannon, Morgan L Fame, Ryann M Fonseca, Erin Mullan, Hillary Johnson, Matthew B Sendamarai, Anoop K Springel, Mark W Laurent, Benoit Lehtinen, Maria K Downregulation of ribosome biogenesis during early forebrain development |
title | Downregulation of ribosome biogenesis during early forebrain development |
title_full | Downregulation of ribosome biogenesis during early forebrain development |
title_fullStr | Downregulation of ribosome biogenesis during early forebrain development |
title_full_unstemmed | Downregulation of ribosome biogenesis during early forebrain development |
title_short | Downregulation of ribosome biogenesis during early forebrain development |
title_sort | downregulation of ribosome biogenesis during early forebrain development |
topic | Neuroscience |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5984036/ https://www.ncbi.nlm.nih.gov/pubmed/29745900 http://dx.doi.org/10.7554/eLife.36998 |
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