Radial glia require PDGFD-PDGFR$β$ signalling in human but not mouse neocortex. Lui, J. H, Nowakowski, T. J, Pollen, A. A, Javaherian, A., Kriegstein, A. R, & Oldham, M. C Nature, 515(7526):264–268, November, 2014. abstract bibtex Evolutionary expansion of the human neocortex underlies many of our unique mental abilities. This expansion has been attributed to the increased proliferative potential of radial glia (RG; neural stem cells) and their subventricular dispersion from the periventricular niche 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 PDGFR$β$, the cognate receptor 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-PDGFR$β$ 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 PDGFR$β$ in developing mouse neocortex increases the proportion of RG and their subventricular dispersion. These findings highlight the requirement of PDGFD-PDGFR$β$ 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.
@ARTICLE{Lui2014-qa,
title = "Radial glia require {PDGFD-PDGFR$\beta$} signalling in human but
not mouse neocortex",
author = "Lui, Jan H and Nowakowski, Tomasz J and Pollen, Alex A and
Javaherian, Ashkan and Kriegstein, Arnold R and Oldham, Michael C",
abstract = "Evolutionary expansion of the human neocortex underlies many of
our unique mental abilities. This expansion has been attributed
to the increased proliferative potential of radial glia (RG;
neural stem cells) and their subventricular dispersion from the
periventricular niche 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
PDGFR$\beta$, the cognate receptor 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-PDGFR$\beta$ 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 PDGFR$\beta$ in developing mouse
neocortex increases the proportion of RG and their subventricular
dispersion. These findings highlight the requirement of
PDGFD-PDGFR$\beta$ 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.",
journal = "Nature",
volume = 515,
number = 7526,
pages = "264--268",
month = nov,
year = 2014,
language = "en"
}
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C"],"bibdata":{"bibtype":"article","type":"article","title":"Radial glia require PDGFD-PDGFR$β$ signalling in human but not mouse neocortex","author":[{"propositions":[],"lastnames":["Lui"],"firstnames":["Jan","H"],"suffixes":[]},{"propositions":[],"lastnames":["Nowakowski"],"firstnames":["Tomasz","J"],"suffixes":[]},{"propositions":[],"lastnames":["Pollen"],"firstnames":["Alex","A"],"suffixes":[]},{"propositions":[],"lastnames":["Javaherian"],"firstnames":["Ashkan"],"suffixes":[]},{"propositions":[],"lastnames":["Kriegstein"],"firstnames":["Arnold","R"],"suffixes":[]},{"propositions":[],"lastnames":["Oldham"],"firstnames":["Michael","C"],"suffixes":[]}],"abstract":"Evolutionary expansion of the human neocortex underlies many of our unique mental abilities. This expansion has been attributed to the increased proliferative potential of radial glia (RG; neural stem cells) and their subventricular dispersion from the periventricular niche 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 PDGFR$β$, the cognate receptor 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-PDGFR$β$ 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 PDGFR$β$ in developing mouse neocortex increases the proportion of RG and their subventricular dispersion. These findings highlight the requirement of PDGFD-PDGFR$β$ 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.","journal":"Nature","volume":"515","number":"7526","pages":"264–268","month":"November","year":"2014","language":"en","bibtex":"@ARTICLE{Lui2014-qa,\n title = \"Radial glia require {PDGFD-PDGFR$\\beta$} signalling in human but\n not mouse neocortex\",\n author = \"Lui, Jan H and Nowakowski, Tomasz J and Pollen, Alex A and\n Javaherian, Ashkan and Kriegstein, Arnold R and Oldham, Michael C\",\n abstract = \"Evolutionary expansion of the human neocortex underlies many of\n our unique mental abilities. This expansion has been attributed\n to the increased proliferative potential of radial glia (RG;\n neural stem cells) and their subventricular dispersion from the\n periventricular niche during neocortical development. Such\n adaptations may have evolved through gene expression changes in\n RG. However, whether or how RG gene expression varies between\n humans and other species is unknown. Here we show that the\n transcriptional profiles of human and mouse neocortical RG are\n broadly conserved during neurogenesis, yet diverge for specific\n signalling pathways. By analysing differential gene co-expression\n relationships between the species, we demonstrate that the growth\n factor PDGFD is specifically expressed by RG in human, but not\n mouse, corticogenesis. We also show that the expression domain of\n PDGFR$\\beta$, the cognate receptor for PDGFD, is evolutionarily\n divergent, with high expression in the germinal region of dorsal\n human neocortex but not in the mouse. Pharmacological inhibition\n of PDGFD-PDGFR$\\beta$ signalling in slice culture prevents normal\n cell cycle progression of neocortical RG in human, but not mouse.\n Conversely, injection of recombinant PDGFD or ectopic expression\n of constitutively active PDGFR$\\beta$ in developing mouse\n neocortex increases the proportion of RG and their subventricular\n dispersion. These findings highlight the requirement of\n PDGFD-PDGFR$\\beta$ signalling for human neocortical development\n and suggest that local production of growth factors by RG\n supports the expanded germinal region and progenitor\n heterogeneity of species with large brains.\",\n journal = \"Nature\",\n volume = 515,\n number = 7526,\n pages = \"264--268\",\n month = nov,\n year = 2014,\n language = \"en\"\n}\n\n","author_short":["Lui, J. H","Nowakowski, T. J","Pollen, A. A","Javaherian, A.","Kriegstein, A. R","Oldham, M. 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