scholarly journals Dorsal-to-ventral neocortical expansion is physically primed by ventral streaming of early embryonic preplate neurons

2019 ◽  
Author(s):  
Kanako Saito ◽  
Mayumi Okamoto ◽  
Yuto Watanabe ◽  
Namiko Noguchi ◽  
Arata Nagasaka ◽  
...  
Keyword(s):  
Molecular Mechanisms ◽  
Cortical Plate ◽  
Lateral Region ◽  
Somatotopic Map ◽  
Radial Glial

SummaryMammalian neocortex exhibits a disproportionally “luxurious” representation of somatotopies in its lateral region, which depends on dorsal-to-ventral expansion of the pallium during development. Despite recent studies elucidating the molecular mechanisms underlying the cortical arealization/patterning, we know very little about how the cortex expands ventrally and the nature of the underlying force-generating events. We found that neurons born earliest (at embryonic day 10 [E10]) in the mouse pallium migrated ventrally and then extended corticofugal axons, which together formed a morphogenetic flow of the preplate that persists until E13. These neurons exerted pulling and pushing forces at the process and the soma, respectively. Ablation of these E10-born neurons attenuated both deflection of radial glial fibers (by E13) and extension of the cortical plate (by E14), which should occur ventrally, and subsequently shrank the postnatal neocortical map dorsally. This previously unrecognized preplate stream physically primes neocortical expansion and somatotopic map formation.

scholarly journals Control of neurogenic competence in mammalian hypothalamic tanycytes

2021 ◽  
Vol 7 (22) ◽  
pp. eabg3777
Author(s):  
Sooyeon Yoo ◽  
Juhyun Kim ◽  
Pin Lyu ◽  
Thanh V. Hoang ◽  
Alex Ma ◽  
...  
Keyword(s):  
Single Cell ◽  
Molecular Mechanisms ◽  
Radial Glial Cells ◽  
Neuronal Progenitors ◽  
Physiological Processes ◽  
Internal States ◽  
Nuclear Factor I ◽  
Radial Glial ◽  
Accessible Chromatin ◽  
Deficient Mice

Hypothalamic tanycytes, radial glial cells that share many features with neuronal progenitors, can generate small numbers of neurons in the postnatal hypothalamus, but the identity of these neurons and the molecular mechanisms that control tanycyte-derived neurogenesis are unknown. In this study, we show that tanycyte-specific disruption of the NFI family of transcription factors (Nfia/b/x) robustly stimulates tanycyte proliferation and tanycyte-derived neurogenesis. Single-cell RNA sequencing (scRNA-seq) and single-cell assay for transposase-accessible chromatin sequencing (scATAC-seq) analysis reveals that NFI (nuclear factor I) factors repress Sonic hedgehog (Shh) and Wnt signaling in tanycytes and modulation of these pathways blocks proliferation and tanycyte-derived neurogenesis in Nfia/b/x-deficient mice. Nfia/b/x-deficient tanycytes give rise to multiple mediobasal hypothalamic neuronal subtypes that can mature, fire action potentials, receive synaptic inputs, and selectively respond to changes in internal states. These findings identify molecular mechanisms that control tanycyte-derived neurogenesis, which can potentially be targeted to selectively remodel the hypothalamic neural circuitry that controls homeostatic physiological processes.

scholarly journals Control of neurogenic competence in mammalian hypothalamic tanycytes

2020 ◽  
Author(s):  
Sooyeon Yoo ◽  
Juhyun Kim ◽  
Pin Lyu ◽  
Thanh V. Hoang ◽  
Alex Ma ◽  
...  
Keyword(s):  
Transcription Factors ◽  
Molecular Mechanisms ◽  
Neural Circuitry ◽  
Radial Glial Cells ◽  
Neuronal Progenitors ◽  
Physiological Processes ◽  
Internal States ◽  
Radial Glial ◽  
Synaptic Circuitry ◽  
Deficient Mice

AbstractHypothalamic tanycytes, radial glial cells that share many features with neuronal progenitors, generate small numbers of neurons in the postnatal hypothalamus, but the identity of these neurons and the molecular mechanisms that control tanycyte-derived neurogenesis are unknown. In this study, we demonstrate that tanycyte-specific disruption of the NFI family of transcription factors (Nfia/b/x) robustly stimulates tanycyte proliferation and tanycyte-derived neurogenesis. Single-cell RNA- and ATAC-Seq analysis reveals that NFI factors repress Shh and Wnt signaling in tanycytes, and small molecule modulation of these pathways blocks proliferation and tanycyte-derived neurogenesis in Nfia/b/x-deficient mice. We show that Nfia/b/x-deficient tanycytes give rise to multiple mediobasal hypothalamic neuronal subtypes that can mature, integrate into hypothalamic synaptic circuitry, and selectively respond to changes in internal states. These findings identify molecular mechanisms that control tanycyte-derived neurogenesis, suggesting a new therapeutic approach to selectively remodel the hypothalamic neural circuitry that controls homeostatic physiological processes.

scholarly journals Restoration of the defect in radial glial fiber cell migration and cortical plate organization in brain organoid model of Fukuyama muscular dystrophy.

iScience ◽  
2021 ◽  
pp. 103140
Author(s):  
Mariko Taniguchi-Ikeda ◽  
Michiyo Koyanagi-Aoi ◽  
Tatsuo Maruyama ◽  
Toru Takaori ◽  
Akiko Hosoya ◽  
...  
Keyword(s):  
Cell Migration ◽  
Muscular Dystrophy ◽  
Fiber Cell ◽  
Cortical Plate ◽  
Radial Glial ◽  
Brain Organoid

scholarly journals PDK1–Akt pathway regulates radial neuronal migration and microtubules in the developing mouse neocortex

2016 ◽  
Vol 113 (21) ◽  
pp. E2955-E2964 ◽  
Author(s):  
Yasuhiro Itoh ◽  
Maiko Higuchi ◽  
Koji Oishi ◽  
Yusuke Kishi ◽  
Tomohiko Okazaki ◽  
...  
Keyword(s):  
Neuronal Migration ◽  
Molecular Mechanisms ◽  
Radial Glia ◽  
Radial Distance ◽  
Cytoplasmic Dynein ◽  
Cortical Plate ◽  
Akt Pathway ◽  
Saltatory Movement ◽  
Dependent Protein ◽  
Intermediate Chain

Neurons migrate a long radial distance by a process known as locomotion in the developing mammalian neocortex. During locomotion, immature neurons undergo saltatory movement along radial glia fibers. The molecular mechanisms that regulate the speed of locomotion are largely unknown. We now show that the serine/threonine kinase Akt and its activator phosphoinositide-dependent protein kinase 1 (PDK1) regulate the speed of locomotion of mouse neocortical neurons through the cortical plate. Inactivation of the PDK1–Akt pathway impaired the coordinated movement of the nucleus and centrosome, a microtubule-dependent process, during neuronal migration. Moreover, the PDK1–Akt pathway was found to control microtubules, likely by regulating the binding of accessory proteins including the dynactin subunit p150glued. Consistent with this notion, we found that PDK1 regulates the expression of cytoplasmic dynein intermediate chain and light intermediate chain at a posttranscriptional level in the developing neocortex. Our results thus reveal an essential role for the PDK1–Akt pathway in the regulation of a key step of neuronal migration.

Radial Glial Cell-Derived VCAM1 Regulates Cortical Angiogenesis Through Distinct Enrichments in the Proximal and Distal Radial Processes

2020 ◽  
Vol 30 (6) ◽  
pp. 3717-3730
Author(s):  
Sanguo Zhang ◽  
Huanhuan Joyce Wang ◽  
Jia Li ◽  
Xiao-Ling Hu ◽  
Qin Shen
Keyword(s):  
Blood Vessels ◽  
Radial Glia ◽  
Ventricular Zone ◽  
Mitotic Cell ◽  
Cortical Plate ◽  
Endothelial Cell Proliferation ◽  
Dependent Manner ◽  
Concentration Dependent Manner ◽  
Radial Glial

Abstract Angiogenesis in the developing cerebral cortex accompanies cortical neurogenesis. However, the precise mechanisms underlying cortical angiogenesis at the embryonic stage remain largely unknown. Here, we show that radial glia-derived vascular cell adhesion molecule 1 (VCAM1) coordinates cortical vascularization through different enrichments in the proximal and distal radial glial processes. We found that VCAM1 was highly enriched around the blood vessels in the inner ventricular zone (VZ), preventing the ingrowth of blood vessels into the mitotic cell layer along the ventricular surface. Disrupting the enrichment of VCAM1 surrounding the blood vessels by a tetraspanin-blocking peptide or conditional deletion of Vcam1 gene in neural progenitor cells increased angiogenesis in the inner VZ. Conversely, VCAM1 expressed in the basal endfeet of radial glial processes promoted angiogenic sprouting from the perineural vascular plexus (PNVP). In utero, overexpression of VCAM1 increased the vessel density in the cortical plate, while knockdown of Vcam1 accomplished the opposite. In vitro, we observed that VCAM1 bidirectionally affected endothelial cell proliferation in a concentration-dependent manner. Taken together, our findings identify that distinct concentrations of VCAM1 around VZ blood vessels and the PNVP differently organize cortical angiogenesis during late embryogenesis.

scholarly journals The behavior and functions of embryonic microglia

2021 ◽  
Author(s):  
Yuki Hattori
Keyword(s):  
Molecular Mechanisms ◽  
Ventricular Zone ◽  
Developing Brain ◽  
Embryonic Stage ◽  
Cortical Plate ◽  
Dependent Manner ◽  
Neural Lineage ◽  
Early Embryonic Stage ◽  
Migration Capacity ◽  
A Minor

AbstractMicroglia are the resident immune cells of the central nervous system. Microglial progenitors are generated in the yolk sac during the early embryonic stage. Once microglia enter the brain primordium, these cells colonize the structure through migration and proliferation during brain development. Microglia account for a minor population among the total cells that constitute the developing cortex, but they can associate with many surrounding neural lineage cells by extending their filopodia and through their broad migration capacity. Of note, microglia change their distribution in a stage-dependent manner in the developing brain: microglia are homogenously distributed in the pallium in the early and late embryonic stages, whereas these cells are transiently absent from the cortical plate (CP) from embryonic day (E) 15 to E16 and colonize the ventricular zone (VZ), subventricular zone (SVZ), and intermediate zone (IZ). Previous studies have reported that microglia positioned in the VZ/SVZ/IZ play multiple roles in neural lineage cells, such as regulating neurogenesis, cell survival and neuronal circuit formation. In addition to microglial functions in the zones in which microglia are replenished, these cells indirectly contribute to the proper maturation of post-migratory neurons by exiting the CP during the mid-embryonic stage. Overall, microglial time-dependent distributional changes are necessary to provide particular functions that are required in specific regions. This review summarizes recent advances in the understanding of microglial colonization and multifaceted functions in the developing brain, especially focusing on the embryonic stage, and discuss the molecular mechanisms underlying microglial behaviors.

scholarly journals Cannabinoid Type 1 Receptor is Undetectable in Rodent and Primate Cerebral Neural Stem Cells but Participates in Radial Neuronal Migration

2020 ◽  
Vol 21 (22) ◽  
pp. 8657
Author(s):  
Yury M. Morozov ◽  
Ken Mackie ◽  
Pasko Rakic
Keyword(s):  
Stem Cells ◽  
Cerebral Cortex ◽  
Neural Stem Cells ◽  
Molecular Mechanisms ◽  
Cellular Proliferation ◽  
Cortical Plate ◽  
Projection Neurons ◽  
Embryonic Mouse ◽  
Cannabinoid Type 1 Receptor

Cannabinoid type 1 receptor (CB1R) is expressed and participates in several aspects of cerebral cortex embryonic development as demonstrated with whole-transcriptome mRNA sequencing and other contemporary methods. However, the cellular location of CB1R, which helps to specify molecular mechanisms, remains to be documented. Using three-dimensional (3D) electron microscopic reconstruction, we examined CB1R immunolabeling in proliferating neural stem cells (NSCs) and migrating neurons in the embryonic mouse (Mus musculus) and rhesus macaque (Macaca mulatta) cerebral cortex. We found that the mitotic and postmitotic ventricular and subventricular zone (VZ and SVZ) cells are immunonegative in both species while radially migrating neurons in the intermediate zone (IZ) and cortical plate (CP) contain CB1R-positive intracellular vesicles. CB1R immunolabeling was more numerous and more extensive in monkeys compared to mice. In CB1R-knock out mice, projection neurons in the IZ show migration abnormalities such as an increased number of lateral processes. Thus, in radially migrating neurons CB1R provides a molecular substrate for the regulation of cell movement. Undetectable level of CB1R in VZ/SVZ cells indicates that previously suggested direct CB1R-transmitted regulation of cellular proliferation and fate determination demands rigorous re-examination. More abundant CB1R expression in monkey compared to mouse suggests that therapeutic or recreational cannabis use may be more distressing for immature primate neurons than inferred from experiments with rodents.

Transcription factor/DNA interactions visualized by electron spectroscopic imaging

1992 ◽  
Vol 50 (1) ◽  
pp. 450-451
Author(s):  
David P. Bazett-Jones ◽  
Mark L. Brown
Keyword(s):  
Transcription Factor ◽  
Dna Sequences ◽  
Transcription Initiation ◽  
Molecular Mechanisms ◽  
Phosphorus Content ◽  
Spectroscopic Imaging ◽  
Electron Spectroscopic Imaging ◽  
Dna Backbone ◽  
Two Parameters ◽  
High Level

A multisubunit RNA polymerase enzyme is ultimately responsible for transcription initiation and elongation of RNA, but recognition of the proper start site by the enzyme is regulated by general, temporal and gene-specific trans-factors interacting at promoter and enhancer DNA sequences. To understand the molecular mechanisms which precisely regulate the transcription initiation event, it is crucial to elucidate the structure of the transcription factor/DNA complexes involved. Electron spectroscopic imaging (ESI) provides the opportunity to visualize individual DNA molecules. Enhancement of DNA contrast with ESI is accomplished by imaging with electrons that have interacted with inner shell electrons of phosphorus in the DNA backbone. Phosphorus detection at this intermediately high level of resolution (≈lnm) permits selective imaging of the DNA, to determine whether the protein factors compact, bend or wrap the DNA. Simultaneously, mass analysis and phosphorus content can be measured quantitatively, using adjacent DNA or tobacco mosaic virus (TMV) as mass and phosphorus standards. These two parameters provide stoichiometric information relating the ratios of protein:DNA content.

Dissection of the molecular mechanisms of protein targeting to the peroxisome using immunofluorescence and immunocryoelectron microscopies

1990 ◽  
Vol 48 (3) ◽  
pp. 44-45
Author(s):  
G-A. Keller ◽  
S. J. Gould ◽  
S. Subramani ◽  
S. Krisans
Keyword(s):  
Mammalian Cells ◽  
Molecular Mechanisms ◽  
Protein Targeting ◽  
Firefly Luciferase ◽  
Peroxisomal Enzyme ◽  
Transfected Cells ◽  
Peroxisomal Targeting ◽  
Targeting Signal ◽  
Series Of Experiments ◽  
Peroxisomal Targeting Signal

Subcellular compartments within eukaryotic cells must each be supplied with unique sets of proteins that must be directed to, and translocated across one or more membranes of the target organelles. This transport is mediated by cis- acting targeting signals present within the imported proteins. The following is a chronological account of a series of experiments designed and carried out in an effort to understand how proteins are targeted to the peroxisomal compartment.-We demonstrated by immunocryoelectron microscopy that the enzyme luciferase is a peroxisomal enzyme in the firefly lantern. -We expressed the cDNA encoding firefly luciferase in mammalian cells and demonstrated by immunofluorescence that the enzyme was transported into the peroxisomes of the transfected cells. -Using deletions, linker insertions, and gene fusion to identify regions of luciferase involved in its transport to the peroxisomes, we demonstrated that luciferase contains a peroxisomal targeting signal (PTS) within its COOH-terminal twelve amino acid.

High resolution mapping of nucleic acid containing complexes in vitro and in situ

1996 ◽  
Vol 54 ◽  
pp. 48-49
Author(s):  
D. P. Bazett-Jones ◽  
M. J. Hendzel
Keyword(s):  
Nucleic Acid ◽  
High Resolution ◽  
Transcription Initiation ◽  
Molecular Mechanisms ◽  
Heavy Atom ◽  
Regulation Of Transcription ◽  
High Exposure ◽  
Resolution Mapping ◽  
Tata Sequence

Structural analysis of combinations of nucleosomes and transcription factors on promoter and enhancer elements is necessary in order to understand the molecular mechanisms responsible for the regulation of transcription initiation. Such complexes are often not amenable to study by high resolution crystallographic techniques. We have been applying electron spectroscopic imaging (ESI) to specific problems in molecular biology related to transcription regulation. There are several advantages that this technique offers in studies of nucleoprotein complexes. First, an intermediate level of spatial resolution can be achieved because heavy atom contrast agents are not necessary. Second, mass and stoichiometric relationships of protein and nucleic acid can be estimated by phosphorus detection, an element in much higher proportions in nucleic acid than protein. Third, wrapping or bending of the DNA by the protein constituents can be observed by phosphorus mapping of the complexes. Even when ESI is used with high exposure of electrons to the specimen, important macromolecular information may be provided. For example, an image of the TATA binding protein (TBP) bound to DNA is shown in the Figure (top panel). It can be seen that the protein distorts the DNA away from itself and much of its mass sits off the DNA helix axis. Moreover, phosphorus and mass estimates demonstrate whether one or two TBP molecules interact with this particular promoter TATA sequence.

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