Evolution and cell-type specificity of human-specific genes preferentially expressed in progenitors of fetal neocortex
Understanding the molecular basis that underlies the expansion of the neocortex during primate, and notably human, evolution requires the identification of genes that are particularly active in the neural stem and progenitor cells of the developing neocortex. Here, we have used existing transcriptome datasets to carry out a comprehensive screen for protein-coding genes preferentially expressed in progenitors of fetal human neocortex. We show that fifteen human-specific genes exhibit such expression, and many of them evolved distinct neural progenitor cell-type expression profiles and levels compared to their ancestral paralogs. Functional studies on one such gene, NOTCH2NL, demonstrate its ability to promote basal progenitor proliferation in mice. An additional 35 human genes with progenitor-enriched expression are shown to have orthologs only in primates. Our study provides a resource of genes that are promising candidates to exert specific, and novel, roles in neocortical development during primate, and notably human, evolution.
Transcriptional landscape of the prenatal human brainAvailable at the Allen Brain Atlas.
Molecular Identity of Human Outer Radial Glia Cells During Cortical DevelopmentdbGaP Study Accession: phs000989.v1.p1.
Article and author information
- Wieland B Huttner
- Michael Hiller
Deutsche Forschungsgemeinschaft (SFB655 A2)
- Wieland B Huttner
European Research Council (250197)
- Wieland B Huttner
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Animal experimentation: All animal experiments were performed in accordance with German animal welfare laws and overseen by the institutional review board (reference number TVV2015/05). C57BL/6J mice were maintained in specific pathogen-free conditions in the MPI-CBG animal facility.
Human subjects: Human fetal brain tissue (12-13 weeks post conception (wpc)) was obtained from the Klinik und Poliklinik für Frauenheilkunde und Geburtshilfe, Universitätsklinikum Carl Gustav Carus of the Technische Universität Dresden with informed written maternal consent followed by elective pregnancy termination. Research involving human tissue was approved by the Ethical Review Committee of the Universitätsklinikum Carl Gustav Carus of the Technische Universität Dresden (reference number: EK100052004). In addition, research was approved by the Institutional Review Board of the Max Planck Institute of Molecular Cell Biology and Genetics.
- Joseph G Gleeson, Howard Hughes Medical Institute, The Rockefeller University, United States
- Received: September 27, 2017
- Accepted: March 9, 2018
- Accepted Manuscript published: March 21, 2018 (version 1)
- Version of Record published: April 13, 2018 (version 2)
© 2018, Florio et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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