Radial ‘glial’ progenitors: neurogenesis and signaling

2005 ◽  
Vol 15 (1) ◽  
pp. 29-33 ◽  
Author(s):  
Leah Ever ◽  
Nicholas Gaiano
Keyword(s):  
Glial Progenitors ◽  
Radial Glial

scholarly journals Distinct progenitor behavior underlying neocortical gliogenesis related to tumorigenesis

2020 ◽  
Author(s):  
Zhongfu Shen ◽  
Yang Lin ◽  
Jiajun Yang ◽  
David J. Jörg ◽  
Yuwei Peng ◽  
...  
Keyword(s):  
Progenitor Cell ◽  
Neurofibromatosis Type ◽  
Primary Brain Tumor ◽  
Precursor Cells ◽  
Cell Behavior ◽  
Neocortical Neurons ◽  
Glial Progenitors ◽  
Radial Glial ◽  
Oligodendrocyte Precursor

SUMMARYRadial glial progenitors (RGPs) are responsible for producing the vast majority of neurons and glia in the neocortex. While RGP behavior and progressive generation of neocortical neurons have been delineated, the exact process of neocortical gliogenesis remains elusive. Here, we report the precise progenitor cell behavior and gliogenesis program at single-cell resolution in the mouse neocortex. RGPs transition from neurogenesis to gliogenesis progressively, producing astrocytes, oligodendrocytes, or both in well-defined propensities of 60%:15%:25%, respectively, via fate-restricted “intermediate” precursor cells. While the total number of precursor cells generated by individual RGPs appears stochastic, the output of individual precursor cells exhibit clear patterns in number and subtype, and form discrete local subclusters. Clonal loss of tumor suppressor Neurofibromatosis type 1 leads to excessive production of glia selectively, especially oligodendrocyte precursor cells. These results delineate the cellular program of neocortical gliogenesis quantitatively and suggest the cellular and lineage origin of primary brain tumor.

Loss of PP2A Disrupts the Retention of Radial Glial Progenitors in the Telencephalic Niche to Impair the Generation for Late-Born Neurons During Cortical Development†

2020 ◽  
Vol 30 (7) ◽  
pp. 4183-4196
Author(s):  
Chaoli Huang ◽  
Tingting Liu ◽  
Qihui Wang ◽  
Weikang Hou ◽  
Cuihua Zhou ◽  
...  
Keyword(s):  
Neural Progenitor Cells ◽  
Ventricular Zone ◽  
Cortical Development ◽  
Underlying Mechanism ◽  
Conditional Knockout ◽  
Glial Progenitors ◽  
Radial Glial ◽  
Vitro Analysis ◽  
The Impact

Abstract Telencephalic radial glial progenitors (RGPs) are retained in the ventricular zone (VZ), the niche for neural stem cells during cortical development. However, the underlying mechanism is not well understood. To study whether protein phosphatase 2A (PP2A) may regulate the above process, we generate Ppp2cα conditional knockout (cKO) mice, in which PP2A catalytic subunit α (PP2Acα) is inactivated in neural progenitor cells in the dorsal telencephalon. We show that RGPs are ectopically distributed in cortical areas outside of the VZ in Ppp2cα cKO embryos. Whereas deletion of PP2Acα does not affect the proliferation of RGPs, it significantly impairs the generation of late-born neurons. We find complete loss of apical adherens junctions (AJs) in the ventricular membrane in Ppp2cα cKO cortices. We observe abundant colocalization for N-cadherin and PP2Acα in control AJs. Moreover, in vitro analysis reveals direct interactions of N-cadherin to PP2Acα and to β-catenin. Overall, this study not only uncovers a novel function of PP2Acα in retaining RGPs into the VZ but also demonstrates the impact of PP2A-dependent retention of RGPs on the generation for late-born neurons.

scholarly journals Subset of early radial glial progenitors that contribute to the development of callosal neurons is absent from avian brain

2015 ◽  
Vol 112 (36) ◽  
pp. E5058-E5067 ◽  
Author(s):  
Fernando García-Moreno ◽  
Zoltán Molnár
Keyword(s):  
Pyramidal Neurons ◽  
Large Population ◽  
Homeobox Gene ◽  
Vertebrate Species ◽  
Avian Brain ◽  
Radial Glial Cells ◽  
Glial Progenitors ◽  
Chick Forebrain ◽  
Radial Glial ◽  
Fate Restriction

The classical view of mammalian cortical development suggests that pyramidal neurons are generated in a temporal sequence, with all radial glial cells (RGCs) contributing to both lower and upper neocortical layers. A recent opposing proposal suggests there is a subgroup of fate-restricted RGCs in the early neocortex, which generates only upper-layer neurons. Little is known about the existence of fate restriction of homologous progenitors in other vertebrate species. We investigated the lineage of selected Emx2+ [vertebrate homeobox gene related to Drosophila empty spiracles (ems)] RGCs in mouse neocortex and chick forebrain and found evidence for both sequential and fate-restricted programs only in mouse, indicating that these complementary populations coexist in the developing mammalian but not avian brain. Among a large population of sequentially programmed RGCs in the mouse brain, a subset of self-renewing progenitors lack neurogenic potential during the earliest phase of corticogenesis. After a considerable delay, these progenitors generate callosal upper-layer neurons and glia. On the other hand, we found no homologous delayed population in any sectors of the chick forebrain. This finding suggests that neurogenic delay of selected RGCs may be unique to mammals and possibly associated with the evolution of the corpus callosum.

scholarly journals Radial glial lineage progression and differential intermediate progenitor amplification underlie striatal compartments and circuit organization

2018 ◽  
Author(s):  
Sean M. Kelly ◽  
Ricardo Raudales ◽  
Miao He ◽  
Jannifer Lee ◽  
Yongsoo Kim ◽  
...  
Keyword(s):  
Basal Ganglia ◽  
Late Phase ◽  
Projection Neurons ◽  
Limited Capacity ◽  
Indirect Pathway ◽  
Intermediate Progenitors ◽  
Lateral Ganglionic Eminence ◽  
Glial Progenitors ◽  
Radial Glial ◽  
Glial Lineage

SUMMARYThe circuitry of the striatum is characterized by two organizational plans: the division into striosome and matrix compartments, thought to mediate evaluation and action, and the direct and indirect pathways, thought to promote or suppress behavior. The developmental origins of and relationships between these organizations are unknown, leaving a conceptual gap in understanding the cortico-basal ganglia system. Through genetic fate mapping, we demonstrate that striosome-matrix compartmentalization arises from a lineage program embedded in lateral ganglionic eminence radial glial progenitors mediating neurogenesis through two distinct types of intermediate progenitors (IPs). The early phase of this program produces striosomal spiny projection neurons (SPNs) through fate-restricted apical IPs (aIPSs) with limited capacity; the late phase produces matrix SPNs through fate-restricted basal IPs (bIPMs) with expanded capacity. Remarkably, direct and indirect pathway SPNs arise within both aIPS and bIPM pools, suggesting that striosome-matrix architecture is the fundamental organizational plan of basal ganglia circuitry organization.

scholarly journals A common rule governing differentiation kinetics of mouse cortical progenitors

2020 ◽  
Vol 117 (26) ◽  
pp. 15221-15229 ◽  
Author(s):  
Setsuko Sahara ◽  
Takashi Kodama ◽  
Charles F. Stevens
Keyword(s):  
Developmental Trajectory ◽  
Adult Brain ◽  
Self Renewal ◽  
Common Rule ◽  
Proliferation And Differentiation ◽  
Glial Progenitors ◽  
Radial Glial ◽  
Kinetics Of ◽  
Cortical Progenitor

The balance between proliferation and differentiation of stem cells and progenitors determines the size of an adult brain region. While the molecular mechanisms regulating proliferation and differentiation of cortical progenitors have been intensively studied, an analysis of the kinetics of progenitor choice between self-renewal and differentiation in vivo is, due to the technical difficulties, still unknown. Here we established a descriptive mathematical model to estimate the probability of self-renewal or differentiation of cortical progenitor behaviors in vivo, a variable we have termed the expansion coefficient. We have applied the model, one which depends only on experimentally measured parameters, to the developing mouse cortex where the expansive neuroepithelial cells and neurogenic radial glial progenitors are coexisting. Surprisingly, we found that the expansion coefficients of both neuroepithelium cells and radial glial progenitors follow the same developmental trajectory during cortical development, suggesting a common rule governing self-renewal/differentiation behaviors in mouse cortical progenitor differentiation.

scholarly journals Endosomal trafficking defects alter neural progenitor proliferation and cause microcephaly

2020 ◽  
Author(s):  
Jacopo A. Carpentieri ◽  
Amandine Di Cicco ◽  
David Andreau ◽  
Laurence Del Maestro ◽  
Fatima El Marjou ◽  
...  
Keyword(s):  
Brain Size ◽  
Endosomal Trafficking ◽  
Loss Of Function ◽  
Pathway Activation ◽  
Glial Progenitors ◽  
Glial Progenitor Cells ◽  
Important Regulator ◽  
Radial Glial ◽  
Trafficking Defects

AbstractPrimary microcephaly and megalencephaly are severe brain malformations defined by reduced and increased brain size, respectively. Whether these two pathologies arise from related alterations at the molecular level is unclear. Microcephaly has been largely associated with centrosomal defects, leading to cell death. Here, we investigated the consequences of WDR81 loss of function, which cause severe microcephaly in patients. We show that WDR81 regulates endosomal trafficking of EGFR, and that loss of function leads to reduced MAP kinase pathway activation. Mouse radial glial progenitor cells knocked-out for WDR81 display reduced proliferation rates, leading to reduced brain size. These proliferation defects are rescued in vivo by the expression of megalencephaly-causing mutated Cyclin D2. Our results identify the endosomal machinery as an important regulator of RG cell proliferation rates and brain growth. They demonstrate that microcephaly and megalencephaly can be due to opposite effects on the proliferation rate of radial glial progenitors.

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