Analogous mechanism regulating formation of neocortical basal radial glia and cerebellar Bergmann glia

Abstract
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Abstract

Neocortical basal radial glia (bRG) and cerebellar Bergmann glia (BG) are basal progenitors derived from ventricular apical radial glia (aRG) that selectively lose their apical processes. bRG and BG have been implicated in the expansion and folding of the cerebrum and cerebellum, respectively. Here, we analyzed the molecular characteristics and development of bRG and BG. Transcriptomic comparison revealed striking similarity of the molecular features of bRG and BG. We found that heightened ERK signaling activity in aRG is tightly linked to the temporal formation and the relative abundance of bRG in human and mouse cortices. Forced activation of an FGF-ERK-ETV axis that is crucial to BG induction specifically induced bRG with canonical human bRG features in mice. Therefore, our data point to a common mechanism of bRG and BG generation, bearing implications to the role for these basal progenitors in the evolution of cortical folding of the cerebrum and cerebellum.

Data availability

The following data sets were generated

1. James Li
(2016) RNA-seq Analysis of Wild Type and Ptpn11-deficient cerebellar Transcriptomes
Publicly available at the NCBI Gene Expression Omnibus (accession no: GSE87104).

https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE87104

The following previously published data sets were used

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(2011) Transcriptional programs in transient embryonic zones of the cerebral cortex defined by high-resolution mRNA-sequencing
Publicly available at the NCBI Gene Expression Omnibus (accession no: GSE30765).

https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE30765
(2012) Transcriptomes of germinal zones of human and mouse fetal neocortex suggest a role of extracellular matrix in progenitor self-renewal
Publicly available at the NCBI Gene Expression Omnibus (accession no: GSE38805).

https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE38805
(2015) Human-specific gene ARHGAP11B promotes basal progenitor amplification and neocortex expansion
Publicly available at the NCBI Gene Expression Omnibus (accession no: GSE65000).

https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE65000
(2015) Single Cell Analysis Reveals Unexpected Transcriptional Heterogeneity of Neural Progenitors in the Developing Human Cortex
Publicly available at the NCBI Gene Expression Omnibus (accession no: GSE66217).

https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE66217
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3. Yao Z
4. Thomsen ER
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9. Nelson AM
10. Shapovalova NV
11. Ramanathan S
(2015) Fixed single-cell transcriptomic characterization of human radial glial diversity
Publicly available at the NCBI Gene Expression Omnibus (accession no: GSE71858).

https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE71858
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2. Brickman J
(2015) Expression data from mouse embryonic stem cells across a time course of Erk stimulation
Publicly available at the NCBI Gene Expression Omnibus (accession no: GSE59755).

https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE59755

Article and author information

Author details

Xin Heng

Department of Genetics and Genome Sciences, University of Connecticut School of Medicine, Farmington, United States

Competing interests
The authors declare that no competing interests exist.
Qiuxia Guo

Department of Genetics and Genome Sciences, University of Connecticut School of Medicine, Farmington, United States

Competing interests
The authors declare that no competing interests exist.
Alan W Leung

Department of Genetics, Yale University, New Haven, United States

Competing interests
The authors declare that no competing interests exist.
James YH Li

Department of Genetics and Genome Sciences, University of Connecticut School of Medicine, Farmington, United States

For correspondence
jali@uchc.edu

Competing interests
The authors declare that no competing interests exist.

"This ORCID iD identifies the author of this article:" 0000-0002-9231-2698

Funding

National Institutes of Health (R01MH094914)

James YH Li

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Ethics

Animal experimentation: This study was performed in strict accordance with the recommendations in the Guide for the Care and Use of Laboratory Animals of the National Institutes of Health. All of the animals were handled according to approved institutional animal care and use committee (IACUC) protocols (101159-0918) of the University of Connecticut Health. All surgery was performed under sodium pentobarbital anesthesia, and every effort was made to minimize suffering.

Copyright

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.