Reintroduction of the Archaic Variant of in Cortical Organoids Alters Neurodevelopment

Overview

Journal Science

Specialty Science

Date 2021 Feb 12

PMID 33574182

Citations 47

Authors

Cleber A Trujillo

Edward S Rice

Nathan K Schaefer

Isaac A Chaim

Emily C Wheeler

Assael A Madrigal

Justin Buchanan

Sebastian Preissl

Allen Wang

Priscilla D Negraes

Ryan A Szeto

Roberto H Herai

Alik Huseynov

Mariana S A Ferraz

Fernando S Borges

Alexandre H Kihara

Ashley Byrne

Maximillian Marin

Christopher Vollmers

Angela N Brooks

Jonathan D Lautz

Katerina Semendeferi

Beth Shapiro

Gene W Yeo

Stephen E P Smith

Richard E Green

Alysson R Muotri

Affiliations

Soon will be listed here.

Abstract

The evolutionarily conserved splicing regulator neuro-oncological ventral antigen 1 () plays a key role in neural development and function. 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 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 , which is exclusive to modern humans since divergence from Neanderthals, may have had functional consequences for our species' evolution.

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