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FASN-dependent de novo lipogenesis is required for brain development
Fate and behavior of neural progenitor cells are tightly regulated during mammalian brain development. Metabolic pathways, such as glycolysis and oxidative phosphorylation, that are required for supplying energy and providing molecular building blocks to generate cells govern progenitor function. Ho...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
National Academy of Sciences
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8764667/ https://www.ncbi.nlm.nih.gov/pubmed/34996870 http://dx.doi.org/10.1073/pnas.2112040119 |
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author | Gonzalez-Bohorquez, Daniel Gallego López, Isabel M. Jaeger, Baptiste N. Pfammatter, Sibylle Bowers, Megan Semenkovich, Clay F. Jessberger, Sebastian |
author_facet | Gonzalez-Bohorquez, Daniel Gallego López, Isabel M. Jaeger, Baptiste N. Pfammatter, Sibylle Bowers, Megan Semenkovich, Clay F. Jessberger, Sebastian |
author_sort | Gonzalez-Bohorquez, Daniel |
collection | PubMed |
description | Fate and behavior of neural progenitor cells are tightly regulated during mammalian brain development. Metabolic pathways, such as glycolysis and oxidative phosphorylation, that are required for supplying energy and providing molecular building blocks to generate cells govern progenitor function. However, the role of de novo lipogenesis, which is the conversion of glucose into fatty acids through the multienzyme protein fatty acid synthase (FASN), for brain development remains unknown. Using Emx1Cre-mediated, tissue-specific deletion of Fasn in the mouse embryonic telencephalon, we show that loss of FASN causes severe microcephaly, largely due to altered polarity of apical, radial glia progenitors and reduced progenitor proliferation. Furthermore, genetic deletion and pharmacological inhibition of FASN in human embryonic stem cell–derived forebrain organoids identifies a conserved role of FASN-dependent lipogenesis for radial glia cell polarity in human brain organoids. Thus, our data establish a role of de novo lipogenesis for mouse and human brain development and identify a link between progenitor-cell polarity and lipid metabolism. |
format | Online Article Text |
id | pubmed-8764667 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | National Academy of Sciences |
record_format | MEDLINE/PubMed |
spelling | pubmed-87646672022-01-26 FASN-dependent de novo lipogenesis is required for brain development Gonzalez-Bohorquez, Daniel Gallego López, Isabel M. Jaeger, Baptiste N. Pfammatter, Sibylle Bowers, Megan Semenkovich, Clay F. Jessberger, Sebastian Proc Natl Acad Sci U S A Biological Sciences Fate and behavior of neural progenitor cells are tightly regulated during mammalian brain development. Metabolic pathways, such as glycolysis and oxidative phosphorylation, that are required for supplying energy and providing molecular building blocks to generate cells govern progenitor function. However, the role of de novo lipogenesis, which is the conversion of glucose into fatty acids through the multienzyme protein fatty acid synthase (FASN), for brain development remains unknown. Using Emx1Cre-mediated, tissue-specific deletion of Fasn in the mouse embryonic telencephalon, we show that loss of FASN causes severe microcephaly, largely due to altered polarity of apical, radial glia progenitors and reduced progenitor proliferation. Furthermore, genetic deletion and pharmacological inhibition of FASN in human embryonic stem cell–derived forebrain organoids identifies a conserved role of FASN-dependent lipogenesis for radial glia cell polarity in human brain organoids. Thus, our data establish a role of de novo lipogenesis for mouse and human brain development and identify a link between progenitor-cell polarity and lipid metabolism. National Academy of Sciences 2022-01-07 2022-01-11 /pmc/articles/PMC8764667/ /pubmed/34996870 http://dx.doi.org/10.1073/pnas.2112040119 Text en Copyright © 2022 the Author(s). Published by PNAS. https://creativecommons.org/licenses/by/4.0/This open access article is distributed under Creative Commons Attribution License 4.0 (CC BY) (https://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Biological Sciences Gonzalez-Bohorquez, Daniel Gallego López, Isabel M. Jaeger, Baptiste N. Pfammatter, Sibylle Bowers, Megan Semenkovich, Clay F. Jessberger, Sebastian FASN-dependent de novo lipogenesis is required for brain development |
title | FASN-dependent de novo lipogenesis is required for brain development |
title_full | FASN-dependent de novo lipogenesis is required for brain development |
title_fullStr | FASN-dependent de novo lipogenesis is required for brain development |
title_full_unstemmed | FASN-dependent de novo lipogenesis is required for brain development |
title_short | FASN-dependent de novo lipogenesis is required for brain development |
title_sort | fasn-dependent de novo lipogenesis is required for brain development |
topic | Biological Sciences |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8764667/ https://www.ncbi.nlm.nih.gov/pubmed/34996870 http://dx.doi.org/10.1073/pnas.2112040119 |
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