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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

Reintroduction of the archaic variant of NOVA1 in cortical organoids alters neurodevelopment

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Author(s):
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Trujillo, Cleber A. [1, 2] ; Rice, Edward S. [3, 4, 5] ; Schaefer, Nathan K. [3, 6] ; Chaim, Isaac A. [7] ; Wheeler, Emily C. [7] ; Madrigal, Assael A. [7] ; Buchanan, Justin [8] ; Preissl, Sebastian [8] ; Wang, Allen [8] ; Negraes, Priscilla D. [1, 2] ; Szeto, Ryan A. [1, 2] ; Herai, Roberto H. [9] ; Huseynov, Alik [10] ; Ferraz, Mariana S. A. [11] ; Borges, Fernando S. [11] ; Kihara, Alexandre H. [11] ; Byrne, Ashley [12] ; Marin, Maximillian [3, 13] ; Vollmers, Christopher [3] ; Brooks, Angela N. [3] ; Lautz, Jonathan D. [14, 15, 16] ; Semendeferi, Katerina [17] ; Shapiro, Beth [18, 19] ; Yeo, Gene W. [8] ; Smith, Stephen E. P. [14, 15, 16] ; Green, Richard E. [3] ; Muotri, Alysson R. [1, 2]
Total Authors: 27
Affiliation:
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[1] Univ Calif San Diego, Dept Pediat, Sch Med, Kavli Inst Brain & Mind, Ctr Acad Res & Training Anthropogeny CARTA, La Jolla, CA 92037 - USA
[2] Univ Calif San Diego, Dept Cellular & Mol Med, Sch Med, Kavli Inst Brain & Mind, Ctr Acad Res & Training Anthropogeny CARTA, La Jolla, CA 92037 - USA
[3] Univ Calif Santa Cruz, Dept Biomol Engn, Santa Cruz, CA 95064 - USA
[4] Univ Nebraska, Dept Anim Sci, Lincoln, NE 68583 - USA
[5] Univ Missouri, Bond Life Sci Ctr, Columbia, MO 65211 - USA
[6] Univ Calif San Francisco, Eli & Edythe Broad Ctr Regenerat Med & Stern Cell, San Francisco, CA 94143 - USA
[7] Univ Calif San Diego, Sch Med, Dept Cellular & Mol Med, La Jolla, CA 92093 - USA
[8] Univ Calif San Diego, Ctr Epigen, Dept Cellular & Mol Med, La Jolla, CA 92093 - USA
[9] Pontificia Univ Catolica Parana, Sch Med, Expt Multiuser Lab LEM, Grad Program Hlth Sci, BR-80215901 Curitiba, PR - Brazil
[10] Imperial Coll London, Natl Heart & Lung Inst, London SW3 6LY - England
[11] Univ Fed ABC, Ctr Matemat Comp & Cognicao, Lab Neurogenet, BR-09606070 Sao Bernardo Do Campo, SP - Brazil
[12] Univ Calif Santa Cruz, Dept Mol Cell & Dev Biol, Santa Cruz, CA 95064 - USA
[13] Harvard Med Sch, Dept Biomed Informat, Boston, MA - USA
[14] Univ Washington, Dept Pediat, Seattle, WA 98195 - USA
[15] Univ Washington, Grad Program Neurosci, Seattle, WA 98195 - USA
[16] Seattle Childrens Res Inst, Ctr Integrat Brain Res, Seattle, WA 98101 - USA
[17] Univ Calif San Diego, Ctr Acad Res & Training Anthropogeny CARTA, Kavli Inst Brain & Mind, Dept Anthropol, La Jolla, CA 92037 - USA
[18] Univ Calif Santa Cruz, Dept Ecol & Evolutionary Biol, Santa Cruz, CA 95064 - USA
[19] Univ Calif Santa Cruz, Howard Hughes Med Inst, Santa Cruz, CA 95064 - USA
Total Affiliations: 19
Document type: Journal article
Source: Science; v. 371, n. 6530, p. 694+, FEB 12 2021.
Web of Science Citations: 5
Abstract

The evolutionarily conserved splicing regulator neuro-oncological ventral antigen 1 (NOVA1) plays a key role in neural development and function. NOVA1 also includes a protein-coding difference between the modern human genome and Neanderthal and Denisovan genomes. To investigate the functional importance of an amino acid change in humans, we reintroduced the archaic allele into human induced pluripotent cells using genome editing and then followed their neural development through cortical organoids. This modification promoted slower development and higher surface complexity in cortical organoids with the archaic version of NOVA1. Moreover, levels of synaptic markers and synaptic protein coassociations correlated with altered electrophysiological properties in organoids expressing the archaic variant. Our results suggest that the human-specific substitution in NOVA1, which is exclusive to modern humans since divergence from Neanderthals, may have had functional consequences for our species' evolution. (AU)

FAPESP's process: 19/15024-9 - Information flow in neuronal networks of networks: oscillations, criticality and electrical synapses
Grantee:Mariana Sacrini Ayres Ferraz
Support Opportunities: Scholarships in Brazil - Post-Doctoral
FAPESP's process: 19/17892-8 - Degeneration and development of the nervous system: the role of epigenetic processes
Grantee:Alexandre Hiroaki Kihara
Support Opportunities: Regular Research Grants
FAPESP's process: 17/18977-1 - Analysis of Electrical Synapses Contribution in Neuronal Synchronization
Grantee:Fernando da Silva Borges
Support Opportunities: Scholarships in Brazil - Post-Doctoral