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

Autor(es):Mostrar menos -

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]}

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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

• Tipo de documento: Artigo Científico
• Fonte: Science; v. 371, n. 6530, p. 694+, FEB 12 2021.
• Citações Web of Science: 5

Resumo

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)

• Processo FAPESP: 19/15024-9 - Fluxo de informação em rede de redes neuronais: oscilações, criticalidade e sinapses elétricas
• Beneficiário: Mariana Sacrini Ayres Ferraz
• Modalidade de apoio: Bolsas no Brasil - Pós-Doutorado
• Processo FAPESP: 19/17892-8 - Degeneração e desenvolvimento do sistema nervoso: o papel de processos epigenéticos
• Beneficiário: Alexandre Hiroaki Kihara
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 17/18977-1 - Análise da Contribuição das Sinapses Elétricas na Sicronização Neuronal
• Beneficiário: Fernando da Silva Borges
• Modalidade de apoio: Bolsas no Brasil - Pós-Doutorado