Analogous mechanism regulating formation of neocortical basal radial glia and cerebellar Bergmann glia
- University of Connecticut School of Medicine, United States
- Yale University, United States
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
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RNA-seq Analysis of Wild Type and Ptpn11-deficient cerebellar TranscriptomesPublicly available at the NCBI Gene Expression Omnibus (accession no: GSE87104).
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Transcriptional programs in transient embryonic zones of the cerebral cortex defined by high-resolution mRNA-sequencingPublicly available at the NCBI Gene Expression Omnibus (accession no: GSE30765).
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Transcriptomes of germinal zones of human and mouse fetal neocortex suggest a role of extracellular matrix in progenitor self-renewalPublicly available at the NCBI Gene Expression Omnibus (accession no: GSE38805).
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Human-specific gene ARHGAP11B promotes basal progenitor amplification and neocortex expansionPublicly available at the NCBI Gene Expression Omnibus (accession no: GSE65000).
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Single Cell Analysis Reveals Unexpected Transcriptional Heterogeneity of Neural Progenitors in the Developing Human CortexPublicly available at the NCBI Gene Expression Omnibus (accession no: GSE66217).
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Fixed single-cell transcriptomic characterization of human radial glial diversityPublicly available at the NCBI Gene Expression Omnibus (accession no: GSE71858).
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Expression data from mouse embryonic stem cells across a time course of Erk stimulationPublicly available at the NCBI Gene Expression Omnibus (accession no: GSE59755).
Article and author information
Author details
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.
Reviewing Editor
- Constance L Cepko, Howard Hughes Medical Institute, Harvard Medical School, United States
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.
Version history
- Received: November 16, 2016
- Accepted: May 9, 2017
- Accepted Manuscript published: May 10, 2017 (version 1)
- Version of Record published: June 2, 2017 (version 2)
Copyright
© 2017, Heng et al.
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.
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Analogous mechanism regulating formation of neocortical basal radial glia and cerebellar Bergmann glia
eLife 6:e23253.
https://doi.org/10.7554/eLife.23253
Further reading
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During embryogenesis, the fetal liver becomes the main hematopoietic organ, where stem and progenitor cells as well as immature and mature immune cells form an intricate cellular network. Hematopoietic stem cells (HSCs) reside in a specialized niche, which is essential for their proliferation and differentiation. However, the cellular and molecular determinants contributing to this fetal HSC niche remain largely unknown. Macrophages are the first differentiated hematopoietic cells found in the developing liver, where they are important for fetal erythropoiesis by promoting erythrocyte maturation and phagocytosing expelled nuclei. Yet, whether macrophages play a role in fetal hematopoiesis beyond serving as a niche for maturing erythroblasts remains elusive. Here, we investigate the heterogeneity of macrophage populations in the murine fetal liver to define their specific roles during hematopoiesis. Using a single-cell omics approach combined with spatial proteomics and genetic fate-mapping models, we found that fetal liver macrophages cluster into distinct yolk sac-derived subpopulations and that long-term HSCs are interacting preferentially with one of the macrophage subpopulations. Fetal livers lacking macrophages show a delay in erythropoiesis and have an increased number of granulocytes, which can be attributed to transcriptional reprogramming and altered differentiation potential of long-term HSCs. Together, our data provide a detailed map of fetal liver macrophage subpopulations and implicate macrophages as part of the fetal HSC niche.
