Loss of NARS1 impairs progenitor proliferation in cortical brain organoids and leads to microcephaly

Lu Wang; Zhen Li; David Sievert; Desirée E. C. Smith; Marisa I. Mendes; Dillon Y. Chen; Valentina Stanley; Shereen Ghosh; Yulu Wang; Majdi Kara; Ayca Dilruba Aslanger; Rasim O. Rosti; Henry Houlden; Gajja S. Salomons; Joseph G. Gleeson

doi:10.1038/s41467-020-17454-4

Nature Communications (Aug 2020)

Loss of NARS1 impairs progenitor proliferation in cortical brain organoids and leads to microcephaly

Lu Wang,
Zhen Li,
David Sievert,
Desirée E. C. Smith,
Marisa I. Mendes,
Dillon Y. Chen,
Valentina Stanley,
Shereen Ghosh,
Yulu Wang,
Majdi Kara,
Ayca Dilruba Aslanger,
Rasim O. Rosti,
Henry Houlden,
Gajja S. Salomons,
Joseph G. Gleeson

Affiliations

Lu Wang: Department of Neurosciences, Howard Hughes Medical Institute, University of California San Diego
Zhen Li: Department of Neurosciences, Howard Hughes Medical Institute, University of California San Diego
David Sievert: Department of Neurosciences, Howard Hughes Medical Institute, University of California San Diego
Desirée E. C. Smith: Metabolic Unit, Department of Clinical Chemistry, Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam Neuroscience, Amsterdam Gastroenterology & Metabolism
Marisa I. Mendes: Metabolic Unit, Department of Clinical Chemistry, Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam Neuroscience, Amsterdam Gastroenterology & Metabolism
Dillon Y. Chen: Rady Children’s Institute for Genomic Medicine, Rady Children’s Hospital
Valentina Stanley: Department of Neurosciences, Howard Hughes Medical Institute, University of California San Diego
Shereen Ghosh: Department of Neurosciences, Howard Hughes Medical Institute, University of California San Diego
Yulu Wang: Laboratory of Biomanufacturing and Food Engineering, Institute of Food Science and Technology, Chinese Academy of Agricultural Sciences
Majdi Kara: University of Tripoli, Tripoli Children’s Hospital
Ayca Dilruba Aslanger: Department of Medical Genetics, Koç University Hospital
Rasim O. Rosti: Department of Neurosciences, Howard Hughes Medical Institute, University of California San Diego
Henry Houlden: Department of Neuromuscular Disorders, UCL Institute of Neurology
Gajja S. Salomons: Metabolic Unit, Department of Clinical Chemistry, Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam Neuroscience, Amsterdam Gastroenterology & Metabolism
Joseph G. Gleeson: Department of Neurosciences, Howard Hughes Medical Institute, University of California San Diego

DOI: https://doi.org/10.1038/s41467-020-17454-4
Journal volume & issue: Vol. 11, no. 1
pp. 1 – 12

Abstract

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Asparaginyl-tRNA synthetase1 (NARS1) is required for protein synthesis. Here, the authors identify biallelic NARS1 mutations in individuals with microcephaly and neurodevelopmental delay. Cortical brain organoid modeling recapitulates microcephaly characteristics and scRNA-seq reveals a role for NARS1 in radial glial cell proliferation.

Published in Nature Communications

ISSN: 2041-1723 (Online)
Publisher: Nature Portfolio
Country of publisher: United Kingdom
LCC subjects: Science
Website: https://www.nature.com/ncomms/

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