Transcriptional priming as a conserved mechanism of lineage diversification in the developing mouse and human neocortex

How the rich variety of neurons in the nervous system arises from neural stem cells is not well understood. Using single-cell RNA-sequencing and in vivo confirmation, we uncover previously unrecognized neural stem and progenitor cell diversity within the fetal mouse and human neocortex, including multiple types of radial glia and intermediate progenitors. We also observed that transcriptional priming underlies the diversification of a subset of ventricular radial glial cells in both species; genetic fate mapping confirms that the primed radial glial cells generate specific types of basal progenitors and neurons. The different precursor lineages therefore diversify streams of cell production in the developing murine and human neocortex. These data show that transcriptional priming is likely a conserved mechanism of mammalian neural precursor lineage specialization.

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Topical Review: Neuronal Migration in Cortical Development

Journal of Child Neurology ◽

10.1177/08830738040190030201 ◽

2004 ◽

Vol 19 (3) ◽

pp. 274-279

Author(s):

Shigeaki Kanatani ◽

Hidenori Tabata ◽

Kazunori Nakajima

Keyword(s):

Neuronal Migration ◽

Radial Glia ◽

Asymmetric Cell Division ◽

Time Lapse ◽

Radial Glial Cells ◽

Daughter Cells ◽

Radial Glial ◽

Time Lapse Imaging ◽

Mitotic Behavior

Cortical formation in the developing brain is a highly complicated process involving neuronal production (through symmetric or asymmetric cell division) interaction of radial glia with neuronal migration, and multiple modes of neuronal migration. It has been convincingly demonstrated by numerous studies that radial glial cells are neural stem cells. However, the processes by which neurons arise from radial glia and migrate to their final destinations in vivo are not yet fully understood. Recent studies using time-lapse imaging of neuronal migration are giving investigators an increasingly more detailed understanding of the mitotic behavior of radial glia and the migrating behavior of their daughter cells. In this review, we describe recent progress in elucidating neuronal migration in brain formation and how neuronal migration is disturbed by mutations in genes that control this process. ( J Child Neurol 2005;20:274—279).

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Mind Bomb 1-Expressing Intermediate Progenitors Generate Notch Signaling to Maintain Radial Glial Cells

Neuron ◽

10.1016/j.neuron.2008.03.018 ◽

2008 ◽

Vol 58 (4) ◽

pp. 519-531 ◽

Cited By ~ 117

Author(s):

Ki-Jun Yoon ◽

Bon-Kyoung Koo ◽

Sun-Kyoung Im ◽

Hyun-Woo Jeong ◽

Jaewang Ghim ◽

...

Keyword(s):

Notch Signaling ◽

Glial Cells ◽

Radial Glial Cells ◽

Intermediate Progenitors ◽

Radial Glial

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Early evolution of radial glial cells in Bilateria

Proceedings of The Royal Society B Biological Sciences ◽

10.1098/rspb.2017.0743 ◽

2017 ◽

Vol 284 (1859) ◽

pp. 20170743 ◽

Cited By ~ 15

Author(s):

Conrad Helm ◽

Anett Karl ◽

Patrick Beckers ◽

Sabrina Kaul-Strehlow ◽

Elke Ulbricht ◽

...

Keyword(s):

Nervous System ◽

Glial Cells ◽

Radial Glia ◽

Early Evolution ◽

Sensory Cells ◽

Last Common Ancestor ◽

Radial Glial Cells ◽

Antibody Staining ◽

Transmission Electron ◽

Radial Glial

Bilaterians usually possess a central nervous system, composed of neurons and supportive cells called glial cells. Whereas neuronal cells are highly comparable in all these animals, glial cells apparently differ, and in deuterostomes, radial glial cells are found. These particular secretory glial cells may represent the archetype of all (macro) glial cells and have not been reported from protostomes so far. This has caused controversial discussions of whether glial cells represent a homologous bilaterian characteristic or whether they (and thus, centralized nervous systems) evolved convergently in the two main clades of bilaterians. By using histology, transmission electron microscopy, immunolabelling and whole-mount in situ hybridization, we show here that protostomes also possess radial glia-like cells, which are very likely to be homologous to those of deuterostomes. Moreover, our antibody staining indicates that the secretory character of radial glial cells is maintained throughout their various evolutionary adaptations. This implies an early evolution of radial glial cells in the last common ancestor of Protostomia and Deuterostomia. Furthermore, it suggests that an intraepidermal nervous system—composed of sensory cells, neurons and radial glial cells—was probably the plesiomorphic condition in the bilaterian ancestor.

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Nestin down-regulation of cortical radial glia is delayed in rats submitted to recurrent status epilepticus during early postnatal life

Arquivos de Neuro-Psiquiatria ◽

10.1590/s0004-282x2009000400020 ◽

2009 ◽

Vol 67 (3a) ◽

pp. 684-688 ◽

Cited By ~ 3

Author(s):

Carla Alessandra Scorza ◽

Ricardo Mario Arida ◽

Fulvio Alexandre Scorza ◽

Esper Abrão Cavalheiro ◽

Maria da Graça Naffah-Mazzacoratti

Keyword(s):

Status Epilepticus ◽

Glial Cells ◽

Radial Glia ◽

Postnatal Life ◽

Multiple Time ◽

Nestin Expression ◽

Down Regulation ◽

Radial Glial Cells ◽

Radial Glial ◽

Early Postnatal Life

OBJECTIVE: Nestin is temporarily expressed in several tissues during development and it is replaced by other protein types during cell differentiation process. This unique property allows distinguishing between undifferentiated and differentiated cells. This study was delineated to analyze the temporal pattern of nestin expression in cortical radial glial cells of rats during normal development and of rats submitted to recurrent status epilepticus (SE) in early postnatal life (P). METHOD: Experimental rats were submitted to pilocarpine-induced SE on P7-9. The cortical temporal profile of nestin was studied by immunohistochemistry at multiple time points (P9, P10, P12, P16, P30 and P90). RESULTS: We observed delayed nestin down-regulation in experimental rats of P9, P10, P12 and P16 groups. In addition, few radial glial cells were still present only in P21 experimental rats. CONCLUSION: Our results suggested that SE during early postnatal life alters normal maturation during a critical period of brain development.

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Persistent expression of stabilized β-catenin delays maturation of radial glial cells into intermediate progenitors

Developmental Biology ◽

10.1016/j.ydbio.2007.07.013 ◽

2007 ◽

Vol 309 (2) ◽

pp. 285-297 ◽

Cited By ~ 63

Author(s):

Carolyn N. Wrobel ◽

Christopher A. Mutch ◽

Sruthi Swaminathan ◽

Makoto M. Taketo ◽

Anjen Chenn

Keyword(s):

Glial Cells ◽

Radial Glial Cells ◽

Intermediate Progenitors ◽

Radial Glial

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Gliogenic Potential of Single Pallial Radial Glial Cells in Lower Cortical Layers

Cells ◽

10.3390/cells10113237 ◽

2021 ◽

Vol 10 (11) ◽

pp. 3237

Author(s):

Ana Cristina Ojalvo-Sanz ◽

Laura López-Mascaraque

Keyword(s):

Glial Cell ◽

Glial Cells ◽

Lineage Tracing ◽

Genetic Lineage ◽

Neural Cells ◽

Cell Type ◽

Cortical Layers ◽

Radial Glial Cells ◽

Radial Glial

During embryonic development, progenitor cells are progressively restricted in their potential to generate different neural cells. A specific progenitor cell type, the radial glial cells, divides symmetrically and then asymmetrically to produce neurons, astrocytes, oligodendrocytes, and NG2-glia in the cerebral cortex. However, the potential of individual progenitors to form glial lineages remains poorly understood. To further investigate the cell progeny of single pallial GFAP-expressing progenitors, we used the in vivo genetic lineage-tracing method, the UbC-(GFAP-PB)-StarTrack. After targeting those progenitors in embryonic mice brains, we tracked their adult glial progeny in lower cortical layers. Clonal analyses revealed the presence of clones containing sibling cells of either a glial cell type (uniform clones) or two different glial cell types (mixed clones). Further, the clonal size and rostro-caudal cell dispersion of sibling cells differed depending on the cell type. We concluded that pallial E14 neural progenitors are a heterogeneous cell population with respect to which glial cell type they produce, as well as the clonal size of their cell progeny.

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The Complex Simplicity of the Brittle Star Nervous System

10.1101/194316 ◽

2017 ◽

Author(s):

Olga Zueva ◽

Maleana Khoury ◽

Thomas Heinzeller ◽

Daria Mashanova ◽

Vladimir Mashanov

Keyword(s):

Central Nervous System ◽

Nervous System ◽

Glial Cells ◽

Radial Glia ◽

Brittle Star ◽

Specific Cell ◽

Radial Glial Cells ◽

Neuronal Markers ◽

The Central Nervous System ◽

Radial Glial

AbstractBrittle stars (Ophiuroidea, Echinodermata) have been increasingly used in studies of animal behavior, locomotion, regeneration, physiology, and bioluminescence. The success of these studies directly depends on good working knowledge of ophiuroid nervous system. Here, we describe the arm nervous system at different levels of organization: microanatomy of the radial nerve cord and peripheral nerves, neural ultrastructure, and localization of different cell types using specific antibody markers. We standardize the nomenclature of nerves and ganglia and provide an anatomically accurate digital 3D model of the arm nervous system as a reference for future studies. Our results helped identify several general features characteristic to the adult echinoderm nervous system, including the extensive anatomical interconnections between the ectoneural and hyponeural components and neuroepithelial organization of the central nervous system with its supporting scaffold formed by radial glial cells. In addition, we provide further support to the notion that the echinoderm radial glia is a complex and diverse cell population. We also tested the suitability of a range of specific cell-type markers for studies of the brittle star nervous system and established that the radial glial cells are reliably labeled by the ERG1 antibodies, whereas the best neuronal markers are acetylated tubulin, ELAV and synaptotagmin B. The transcription factor Brn1/2/4, a marker of neuronal progenitors, is expressed not only in neurons, but also in a subpopulation of radial glia. For the first time, we describe putative ophiuroid proprioceptors associated with the hyponeural part of the central nervous system.

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Decoding Cortical Glial Cell Development

Neuroscience Bulletin ◽

10.1007/s12264-021-00640-9 ◽

2021 ◽

Author(s):

Xiaosu Li ◽

Guoping Liu ◽

Lin Yang ◽

Zhenmeiyu Li ◽

Zhuangzhi Zhang ◽

...

Keyword(s):

Single Cell ◽

Glial Cell ◽

Glial Cells ◽

Cell Lineage ◽

Gabaergic Interneurons ◽

Rna Seq ◽

Radial Glial Cells ◽

Intermediate Progenitors ◽

Late Embryogenesis ◽

Radial Glial

AbstractMouse cortical radial glial cells (RGCs) are primary neural stem cells that give rise to cortical oligodendrocytes, astrocytes, and olfactory bulb (OB) GABAergic interneurons in late embryogenesis. There are fundamental gaps in understanding how these diverse cell subtypes are generated. Here, by combining single-cell RNA-Seq with intersectional lineage analyses, we show that beginning at around E16.5, neocortical RGCs start to generate ASCL1+EGFR+ apical multipotent intermediate progenitors (MIPCs), which then differentiate into basal MIPCs that express ASCL1, EGFR, OLIG2, and MKI67. These basal MIPCs undergo several rounds of divisions to generate most of the cortical oligodendrocytes and astrocytes and a subpopulation of OB interneurons. Finally, single-cell ATAC-Seq supported our model for the genetic logic underlying the specification and differentiation of cortical glial cells and OB interneurons. Taken together, this work reveals the process of cortical radial glial cell lineage progression and the developmental origins of cortical astrocytes and oligodendrocytes.

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Calcium Signaling in the Cerebellar Radial Glia and Its Association with Morphological Changes during Zebrafish Development

International Journal of Molecular Sciences ◽

10.3390/ijms222413509 ◽

2021 ◽

Vol 22 (24) ◽

pp. 13509

Author(s):

Elizabeth Pereida-Jaramillo ◽

Gabriela B. Gómez-González ◽

Angeles Edith Espino-Saldaña ◽

Ataúlfo Martínez-Torres

Keyword(s):

Calcium Signaling ◽

Glial Cells ◽

Radial Glia ◽

Morphological Changes ◽

Neuronal Cell ◽

Functional Coupling ◽

Calcium Waves ◽

Calcium Activity ◽

Radial Glial Cells ◽

Radial Glial

Radial glial cells are a distinct non-neuronal cell type that, during development, span the entire width of the brain walls of the ventricular system. They play a central role in the origin and placement of neurons, since their processes form structural scaffolds that guide and facilitate neuronal migration. Furthermore, glutamatergic signaling in the radial glia of the adult cerebellum (i.e., Bergmann glia), is crucial for precise motor coordination. Radial glial cells exhibit spontaneous calcium activity and functional coupling spread calcium waves. However, the origin of calcium activity in relation to the ontogeny of cerebellar radial glia has not been widely explored, and many questions remain unanswered regarding the role of radial glia in brain development in health and disease. In this study we used a combination of whole mount immunofluorescence and calcium imaging in transgenic (gfap-GCaMP6s) zebrafish to determine how development of calcium activity is related to morphological changes of the cerebellum. We found that the morphological changes in cerebellar radial glia are quite dynamic; the cells are remarkably larger and more elaborate in their soma size, process length and numbers after 7 days post fertilization. Spontaneous calcium events were scarce during the first 3 days of development and calcium waves appeared on day 5, which is associated with the onset of more complex morphologies of radial glia. Blockage of gap junction coupling inhibited the propagation of calcium waves, but not basal local calcium activity. This work establishes crucial clues in radial glia organization, morphology and calcium signaling during development and provides insight into its role in complex behavioral paradigms.

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Differentiating neurons activate transcription of the brain lipid-binding protein gene in radial glia through a novel regulatory element

Development ◽

10.1242/dev.121.6.1719 ◽

1995 ◽

Vol 121 (6) ◽

pp. 1719-1730 ◽

Cited By ~ 3

Author(s):

L. Feng ◽

N. Heintz

Keyword(s):

Glial Cells ◽

Radial Glia ◽

Lipid Binding ◽

Radial Glial Cell ◽

Specific Element ◽

Radial Glial ◽

And Migration ◽

The Brain

Formation and maintenance of a radial glial scaffold is fundamental for development of the vertebrate central nervous system. In mammals, radial glia arise in the neuroepithelium immediately prior to differentiation and migration of neurons away from the ventricular zones, and they are maintained until neuronal migration subsides. We have previously shown that expression of the brain lipid-binding protein (BLBP) in radial glia throughout the developing CNS is strictly correlated with the differentiation and migration of neurons upon these cells, and that BLBP function is required to maintain differentiation of primary cerebellar glial cells in vitro (Feng, L., Hatten, M. E. and Heintz, N. (1994). Neuron 12, 895–908). In this study, we demonstrate that BLBP transcription in vivo involves multiple regulatory elements, and that the dynamic temporal and spatial pattern of BLBP expression in radial and Bergmann glial cells throughout the developing CNS is programmed by a single radial glial cell-specific element (RGE). Furthermore, we demonstrate that BLBP expression in primary cerebellar glial cells requires coculture with differentiating neurons, and that this induction is regulated by the radial glia-specific element. The fact that transcription of BLBP in response to neurons in vitro and its dynamic regulation in radial glia throughout the CNS in vivo are both controlled by the RGE provides the first direct evidence supporting a role for differentiating neurons in the epigenetic regulation of radial glial cell function in vivo.

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