Evolution and cell-type specificity of human-specific genes preferentially expressed in progenitors of fetal neocortex

Research output: Contribution to journalResearch articleContributedpeer-review

Contributors

  • Marta Florio - , Max Planck Institute of Molecular Cell Biology and Genetics, Harvard University (Author)
  • Michael Heide - , Max Planck Institute of Molecular Cell Biology and Genetics (Author)
  • Anneline Pinson - , Max Planck Institute of Molecular Cell Biology and Genetics (Author)
  • Holger Brandl - , Max Planck Institute of Molecular Cell Biology and Genetics (Author)
  • Mareike Albert - , Gene regulatory mechanisms of neocortex evolution (Junior Research Group), Max Planck Institute of Molecular Cell Biology and Genetics (Author)
  • Sylke Winkler - , Max Planck Institute of Molecular Cell Biology and Genetics (Author)
  • Pauline Wimberger - , Department of Gynecology and Obstetrics, TUD Dresden University of Technology (Author)
  • Wieland B. Huttner - , Max Planck Institute of Molecular Cell Biology and Genetics (Author)
  • Michael Hiller - , Max Planck Institute of Molecular Cell Biology and Genetics, Max-Planck-Institute for the Physics of Complex Systems (Author)

Abstract

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 15 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.

Details

Original languageEnglish
Article numbere32332
JournaleLife
Volume7
Publication statusPublished - 21 Mar 2018
Peer-reviewedYes

External IDs

PubMed 29561261
ORCID /0000-0001-9855-9344/work/142244744