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Abstract

Evolutionary expansion of the human neocortex underlies many of our unique mental abilities. This expansion has been attributed to the increased proliferative potential1,2 of radial glia (RG; neural stem cells) and their subventricular dispersion from the periventricular niche3-5 during neocortical development. Such adaptations may have evolved through gene expression changes in RG. However, whether or how RG gene expression varies between humans and other species is unknown. Here we show that the transcriptional profiles of human and mouse neocortical RG are broadly conserved during neurogenesis, yet diverge for specific signalling pathways. By analysing differential gene co-expression relationships between the species, we demonstrate that the growth factor PDGFD is specifically expressed by RG in human, but not mouse, corticogenesis. We also show that the expression domain of PDGFRβ, the cognate receptor6,7 for PDGFD, is evolutionarily divergent, with high expression in the germinal region of dorsal human neocortex but not in the mouse. Pharmacological inhibition of PDGFD-PDGFRβ signalling in slice culture prevents normal cell cycle progression of neocortical RG in human, but not mouse. Conversely, injection of recombinant PDGFD or ectopic expression of constitutively active PDGFRβ in developing mouse neocortex increases the proportion of RG and their subventricular dispersion. These findings highlight the requirement of PDGFD-PDGFRβ signalling for human neocortical development and suggest that local production of growth factors by RG supports the expanded germinal region and progenitor heterogeneity of species with large brains.

Details

10000387
Psychology indexing term
Title
Radial glia require PDGFD-PDGFRb signalling in human but not mouse neocortex
Publication title
Nature; London
Volume
515
Issue
7526
Pages
264-8
Number of pages
15
Publication year
2014
Publication date
Nov 13, 2014
Section
LETTER
Publisher
Nature Publishing Group
Place of publication
London
Country of publication
United States
ISSN
00280836
e-ISSN
14764687
CODEN
NATUAS
Source type
Scholarly Journal
Language of publication
English
Document type
Feature, Journal Article
Document feature
References; Graphs; Diagrams; Photographs; Tables
Accession number
25391964
ProQuest document ID
1628902696
Document URL
https://www.proquest.com/scholarly-journals/radial-glia-require-pdgfd-pdgfrb-signalling-human/docview/1628902696/se-2?accountid=208611
Copyright
Copyright Nature Publishing Group Nov 13, 2014
Last updated
2024-10-04
Database
2 databases
  • ProQuest One Academic
  • ProQuest One Academic