@article {804,
	title = {Loss of NARS1 impairs progenitor proliferation in cortical brain organoids and leads to microcephaly.},
	journal = {Nat Commun},
	volume = {11},
	year = {2020},
	month = {2020 08 12},
	pages = {4038},
	abstract = {<p>Asparaginyl-tRNA synthetase1 (NARS1) is a member of the ubiquitously expressed cytoplasmic Class IIa family of tRNA synthetases required for protein translation. Here, we identify biallelic missense and frameshift mutations in NARS1 in seven patients from three unrelated families with microcephaly and neurodevelopmental delay. Patient cells show reduced NARS1 protein, impaired NARS1 activity and impaired global protein synthesis. Cortical brain organoid modeling shows reduced proliferation of radial glial cells (RGCs), leading to smaller organoids characteristic of microcephaly. Single-cell analysis reveals altered constituents of both astrocytic and RGC lineages, suggesting a requirement for NARS1 in RGC proliferation. Our findings demonstrate that NARS1 is required to meet protein synthetic needs and to support RGC proliferation in human brain development.</p>},
	keywords = {Adolescent, Adult, Aspartate-tRNA Ligase, Base Sequence, Cell Differentiation, Cell Proliferation, Cell Size, Cell Survival, Cerebral Cortex, Child, Family, Female, Fibroblasts, HEK293 Cells, Humans, Induced Pluripotent Stem Cells, Ki-67 Antigen, Male, Microcephaly, Mutation, Neural Stem Cells, Neuroglia, Organoids, Pedigree, RNA, Transfer, Amino Acyl, Young Adult},
	issn = {2041-1723},
	doi = {10.1038/s41467-020-17454-4},
	author = {Wang, Lu and Li, Zhen and Sievert, David and Smith, Desir{\'e}e E C and Mendes, Marisa I and Chen, Dillon Y and Stanley, Valentina and Ghosh, Shereen and Wang, Yulu and Kara, Majdi and Aslanger, Ayca Dilruba and Rosti, Rasim O and Houlden, Henry and Salomons, Gajja S and Gleeson, Joseph G}
}
