Primate-expressed EPIREGULIN promotes basal progenitor proliferation in the developing neocortex

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Abstract

Neocortex expansion during evolution is linked to higher numbers of neurons thought to result from increased proliferative capacity and neurogenic potential of basal progenitor cells (BPs) during development. Here we show that EREG, encoding the growth factor EPIREGULIN, is expressed in the human developing neocortex and in gorilla organoids, but not in the mouse neocortex. Addition of EPIREGULIN to the mouse neocortex increases proliferation of BPs via EGFR-mediated signaling, whereas ablation of EREG in human cortical organoids reduces BP proliferation. Addition of EPIREGULIN to cortical organoids promotes a further increase in proliferation of gorilla but not human BPs. Finally, we identify putative cis-regulatory elements that may contribute to inter-species differences in EREG expression. Overall, our results suggest that species-specific expression of EPIREGULIN may contribute to increased neocortex size in primates by providing a pro-proliferative signal to BPs in the subventricular zone progenitor niche.Competing Interest StatementThe authors have declared no competing interest.

Details

Original languageUndefined
Publication statusPublished - 2023
No renderer: customAssociatesEventsRenderPortal,dk.atira.pure.api.shared.model.researchoutput.WorkingPaper

External IDs

ORCID /0000-0002-1595-5411/work/145695205
ORCID /0000-0001-9599-8632/work/145697455
ORCID /0000-0001-9855-9344/work/145698195
ORCID /0000-0002-4257-2192/work/145698601
ORCID /0000-0002-7157-0372/work/145698613

Keywords