scholarly journals Crucial Roles of the Arp2/3 Complex during Mammalian Corticogenesis

2015 ◽  
Author(s):  
Pei-Shan Wang ◽  
Fu-Sheng Chou ◽  
Fengli Guo ◽  
Praveen Suraneni ◽  
Sheng Xia ◽  
...  
Keyword(s):  
Cell Fate ◽  
Membrane Trafficking ◽  
Neuronal Migration ◽  
Neuronal Cell ◽  
Leading Edge ◽  
Radial Glial Cells ◽  
A Cell ◽  
Radial Glial ◽  
Altered Cell ◽  
Actin Nucleator

The polarity and organization of radial glial cells (RGCs), which serve as both stem cells and scaffolds for neuronal migration, are crucial for cortical development. However, the cytoskeletal mechanisms that drive radial glial outgrowth and maintain RGC polarity remain poorly understood. Here, we show that the Arp2/3 complex, the unique actin nucleator that produces branched actin networks, plays essential roles in RGC polarity and morphogenesis. Disruption of the Arp2/3 complex in RGCs retards process outgrowth toward the basal surface and impairs apical polarity and adherens junctions. Whereas the former is correlated with abnormal actin-based leading edge, the latter is consistent with blockage in membrane trafficking. These defects result in altered cell fate, disrupted cortical lamination and abnormal angiogenesis. In addition, we present evidence that the Arp2/3 complex is a cell-autonomous regulator of neuronal migration. Our data suggest that Arp2/3-mediated actin assembly may be particularly important for neuronal cell motility in soft or poorly adhesive matrix environment.

Topical Review: Neuronal Migration in Cortical Development

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).

Role of GGF/neuregulin signaling in interactions between migrating neurons and radial glia in the developing cerebral cortex

Development ◽  
1997 ◽  
Vol 124 (18) ◽  
pp. 3501-3510 ◽  
Author(s):  
E.S. Anton ◽  
M.A. Marchionni ◽  
K.F. Lee ◽  
P. Rakic
Keyword(s):  
Cerebral Cortex ◽  
Glial Cells ◽  
Neuronal Migration ◽  
Lipid Binding ◽  
Soluble Form ◽  
Dependent Manner ◽  
Radial Glial Cells ◽  
Glial Development ◽  
Radial Glial

During neuronal migration to the developing cerebral cortex, neurons regulate radial glial cell function and radial glial cells, in turn, support neuronal cell migration and differentiation. To study how migrating neurons and radial glial cells influence each others' function in the developing cerebral cortex, we examined the role of glial growth factor (a soluble form of neuregulin), in neuron-radial glial interactions. Here, we show that GGF is expressed by migrating cortical neurons and promotes their migration along radial glial fibers. Concurrently, GGF also promotes the maintenance and elongation of radial glial cells, which are essential for guiding neuronal migration to the cortex. In the absence of GGF signaling via erbB2 receptors, radial glial development is abnormal. Furthermore, GGF's regulation of radial glial development is mediated in part by brain lipid-binding protein (BLBP), a neuronally induced, radial glial molecule, previously shown to be essential for the establishment and maintenance of radial glial fiber system. The ability of GGF to influence both neuronal migration and radial glial development in a mutually dependent manner suggests that it functions as a mediator of interactions between migrating neurons and radial glial cells in the developing cerebral cortex.

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

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.

scholarly journals Development in the Mammalian Auditory System Depends on Transcription Factors

2021 ◽  
Vol 22 (8) ◽  
pp. 4189
Author(s):  
Karen L. Elliott ◽  
Gabriela Pavlínková ◽  
Victor V. Chizhikov ◽  
Ebenezer N. Yamoah ◽  
Bernd Fritzsch
Keyword(s):  
Transcription Factors ◽  
Cell Fate ◽  
Auditory System ◽  
Hair Cells ◽  
System Development ◽  
Neuronal Cell ◽  
Spiral Ganglion Neuron ◽  
Cochlear Hair Cells ◽  
Cochlear Nuclei ◽  
Bhlh Genes

We review the molecular basis of several transcription factors (Eya1, Sox2), including the three related genes coding basic helix–loop–helix (bHLH; see abbreviations) proteins (Neurog1, Neurod1, Atoh1) during the development of spiral ganglia, cochlear nuclei, and cochlear hair cells. Neuronal development requires Neurog1, followed by its downstream target Neurod1, to cross-regulate Atoh1 expression. In contrast, hair cells and cochlear nuclei critically depend on Atoh1 and require Neurod1 expression for interactions with Atoh1. Upregulation of Atoh1 following Neurod1 loss changes some vestibular neurons’ fate into “hair cells”, highlighting the significant interplay between the bHLH genes. Further work showed that replacing Atoh1 by Neurog1 rescues some hair cells from complete absence observed in Atoh1 null mutants, suggesting that bHLH genes can partially replace one another. The inhibition of Atoh1 by Neurod1 is essential for proper neuronal cell fate, and in the absence of Neurod1, Atoh1 is upregulated, resulting in the formation of “intraganglionic” HCs. Additional genes, such as Eya1/Six1, Sox2, Pax2, Gata3, Fgfr2b, Foxg1, and Lmx1a/b, play a role in the auditory system. Finally, both Lmx1a and Lmx1b genes are essential for the cochlear organ of Corti, spiral ganglion neuron, and cochlear nuclei formation. We integrate the mammalian auditory system development to provide comprehensive insights beyond the limited perception driven by singular investigations of cochlear neurons, cochlear hair cells, and cochlear nuclei. A detailed analysis of gene expression is needed to understand better how upstream regulators facilitate gene interactions and mammalian auditory system development.

scholarly journals Syntaxin 1A Gene Is Negatively Regulated in a Cell/Tissue Specific Manner by YY1 Transcription Factor, Which Binds to the −183 to −137 Promoter Region Together with Gene Silencing Factors Including Histone Deacetylase

Biomolecules ◽  
2021 ◽  
Vol 11 (2) ◽  
pp. 146
Author(s):  
Takahiro Nakayama ◽  
Toshiyuki Fukutomi ◽  
Yasuo Terao ◽  
Kimio Akagawa
Keyword(s):  
Transcription Factor ◽  
Gene Silencing ◽  
Protein Complex ◽  
Promoter Region ◽  
Neuronal Cell ◽  
Syntaxin 1A ◽  
Tissue Specific ◽  
Cell Tissue ◽  
Specific Manner ◽  
A Cell

The HPC-1/syntaxin 1A (Stx1a) gene, which is involved in synaptic transmission and neurodevelopmental disorders, is a TATA-less gene with several transcription start sites. It is activated by the binding of Sp1 and acetylated histone H3 to the −204 to +2 core promoter region (CPR) in neuronal cell/tissue. Furthermore, it is depressed by the association of class 1 histone deacetylases (HDACs) to Stx1a–CPR in non-neuronal cell/tissue. To further clarify the factors characterizing Stx1a gene silencing in non-neuronal cell/tissue not expressing Stx1a, we attempted to identify the promoter region forming DNA–protein complex only in non-neuronal cells. Electrophoresis mobility shift assays (EMSA) demonstrated that the −183 to −137 OL2 promoter region forms DNA–protein complex only in non-neuronal fetal rat skin keratinocyte (FRSK) cells which do not express Stx1a. Furthermore, the Yin-Yang 1 (YY1) transcription factor binds to the −183 to −137 promoter region of Stx1a in FRSK cells, as shown by competitive EMSA and supershift assay. Chromatin immunoprecipitation assay revealed that YY1 in vivo associates to Stx1a–CPR in cell/tissue not expressing Stx1a and that trichostatin A treatment in FRSK cells decreases the high-level association of YY1 to Stx1a-CPR in default. Reporter assay indicated that YY1 negatively regulates Stx1a transcription. Finally, mass spectrometry analysis showed that gene silencing factors, including HDAC1, associate onto the −183 to −137 promoter region together with YY1. The current study is the first to report that Stx1a transcription is negatively regulated in a cell/tissue-specific manner by YY1 transcription factor, which binds to the −183 to −137 promoter region together with gene silencing factors, including HDAC.

The functions of Reelin in membrane trafficking and cytoskeletal dynamics: implications for neuronal migration, polarization and differentiation

2017 ◽  
Vol 474 (18) ◽  
pp. 3137-3165 ◽  
Author(s):  
Jessica Santana ◽  
María-Paz Marzolo
Keyword(s):  
Membrane Trafficking ◽  
Neuronal Migration ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Signaling Cascade ◽  
Low Density ◽  
Lipoprotein Receptor ◽  
Density Lipoprotein Receptor ◽  
Reelin Signaling

Reelin is a large extracellular matrix protein with relevant roles in mammalian central nervous system including neurogenesis, neuronal polarization and migration during development; and synaptic plasticity with its implications in learning and memory, in the adult. Dysfunctions in reelin signaling are associated with brain lamination defects such as lissencephaly, but also with neuropsychiatric diseases like autism, schizophrenia and depression as well with neurodegeneration. Reelin signaling involves a core pathway that activates upon reelin binding to its receptors, particularly ApoER2 (apolipoprotein E receptor 2)/LRP8 (low-density lipoprotein receptor-related protein 8) and very low-density lipoprotein receptor, followed by Src/Fyn-mediated phosphorylation of the adaptor protein Dab1 (Disabled-1). Phosphorylated Dab1 (pDab1) is a hub in the signaling cascade, from which several other downstream pathways diverge reflecting the different roles of reelin. Many of these pathways affect the dynamics of the actin and microtubular cytoskeleton, as well as membrane trafficking through the regulation of the activity of small GTPases, including the Rho and Rap families and molecules involved in cell polarity. The complexity of reelin functions is reflected by the fact that, even now, the precise mode of action of this signaling cascade in vivo at the cellular and molecular levels remains unclear. This review addresses and discusses in detail the participation of reelin in the processes underlying neurogenesis, neuronal migration in the cerebral cortex and the hippocampus; and the polarization, differentiation and maturation processes that neurons experiment in order to be functional in the adult brain. In vivo and in vitro evidence is presented in order to facilitate a better understanding of this fascinating system.

Sterol and lipid trafficking in mammalian cells

2006 ◽  
Vol 34 (3) ◽  
pp. 335-339 ◽  
Author(s):  
F.R. Maxfield ◽  
M. Mondal
Keyword(s):  
Membrane Trafficking ◽  
Mammalian Cells ◽  
Intracellular Transport ◽  
Vesicular Transport ◽  
Cholesterol Content ◽  
Cellular Functions ◽  
Lipid Trafficking ◽  
Sterol Transport ◽  
A Cell ◽  
Asymmetrically Distributed

The pathways involved in the intracellular transport and distribution of lipids in general, and sterols in particular, are poorly understood. Cholesterol plays a major role in modulating membrane bilayer structure and important cellular functions, including signal transduction and membrane trafficking. Both the overall cholesterol content of a cell, as well as its distribution in specific organellar membranes are stringently regulated. Several diseases, many of which are incurable at present, have been characterized as results of impaired cholesterol transport and/or storage in the cells. Despite their importance, many fundamental aspects of intracellular sterol transport and distribution are not well understood. For instance, the relative roles of vesicular and non-vesicular transport of cholesterol have not yet been fully determined, nor are the non-vesicular transport mechanisms well characterized. Similarly, whether cholesterol is asymmetrically distributed between the two leaflets of biological membranes, and if so, how this asymmetry is maintained, is poorly understood. In this review, we present a summary of the current understanding of these aspects of intracellular trafficking and distribution of lipids, and more specifically, of sterols.

Reelin is essential for neuronal migration but not for radial glial elongation in neonatal ferret cortex

2008 ◽  
Vol 68 (5) ◽  
pp. 590-604 ◽  
Author(s):  
Alisa Schaefer ◽  
Sylvie Poluch ◽  
Sharon Juliano
Keyword(s):  
Neuronal Migration ◽  
Radial Glial
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