scholarly journals Glycans and glycosaminoglycans in neurobiology: key regulators of neuronal cell function and fate

2018 ◽  
Vol 475 (15) ◽  
pp. 2511-2545 ◽  
Author(s):  
Anthony J. Hayes ◽  
James Melrose
Keyword(s):  
Cell Fate ◽  
Information Transfer ◽  
Cell Function ◽  
Dermatan Sulfate ◽  
Neuronal Cell ◽  
Keratan Sulfate ◽  
Neural Function ◽  
Cellular Survival ◽  
Downstream Signaling ◽  
Blood Group Substances

The aim of the present study was to examine the roles of l-fucose and the glycosaminoglycans (GAGs) keratan sulfate (KS) and chondroitin sulfate/dermatan sulfate (CS/DS) with selected functional molecules in neural tissues. Cell surface glycans and GAGs have evolved over millions of years to become cellular mediators which regulate fundamental aspects of cellular survival. The glycocalyx, which surrounds all cells, actuates responses to growth factors, cytokines and morphogens at the cellular boundary, silencing or activating downstream signaling pathways and gene expression. In this review, we have focused on interactions mediated by l-fucose, KS and CS/DS in the central and peripheral nervous systems. Fucose makes critical contributions in the area of molecular recognition and information transfer in the blood group substances, cytotoxic immunoglobulins, cell fate-mediated Notch-1 interactions, regulation of selectin-mediated neutrophil extravasation in innate immunity and CD-34-mediated new blood vessel development, and the targeting of neuroprogenitor cells to damaged neural tissue. Fucosylated glycoproteins regulate delivery of synaptic neurotransmitters and neural function. Neural KS proteoglycans (PGs) were examined in terms of cellular regulation and their interactive properties with neuroregulatory molecules. The paradoxical properties of CS/DS isomers decorating matrix and transmembrane PGs and the positive and negative regulatory cues they provide to neurons are also discussed.

scholarly journals Transcriptional reprogramming of distinct peripheral sensory neuron subtypes after axonal injury

2019 ◽  
Author(s):  
William Renthal ◽  
Ivan Tochitsky ◽  
Lite Yang ◽  
Yung-Chih Cheng ◽  
Emmy Li ◽  
...  
Keyword(s):  
Cell Fate ◽  
Axonal Regeneration ◽  
Cell Function ◽  
Sensory Information ◽  
Neuronal Cell ◽  
Transcriptional Response ◽  
Cell Identity ◽  
Transcriptional Reprogramming ◽  
Somatosensory Neurons ◽  
Peripheral Sensory

SummaryPrimary somatosensory neurons are specialized to transmit specific types of sensory information through differences in cell size, myelination, and the expression of distinct receptors and ion channels, which together define their transcriptional and functional identity. By transcriptionally profiling sensory ganglia at single-cell resolution, we find that different somatosensory neuronal subtypes undergo a remarkably consistent and dramatic transcriptional response to peripheral nerve injury that both promotes axonal regeneration and suppresses cell identity. Successful axonal regeneration leads to a restoration of neuronal cell identity and the deactivation of the growth program. This injury-induced transcriptional reprogramming requires Atf3, a transcription factor which is induced rapidly after injury and is necessary for axonal regeneration and functional recovery. While Atf3 and other injury-induced transcription factors are known for their role in reprogramming cell fate, their function in mature neurons is likely to facilitate major adaptive changes in cell function in response to damaging environmental stimuli.

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.

split ends encodes large nuclear proteins that regulate neuronal cell fate and axon extension in the Drosophila embryo

Development ◽  
2000 ◽  
Vol 127 (7) ◽  
pp. 1517-1529 ◽  
Author(s):  
B. Kuang ◽  
S.C. Wu ◽  
Y. Shin ◽  
L. Luo ◽  
P. Kolodziej
Keyword(s):  
Cell Fate ◽  
Egf Receptor ◽  
Neuronal Cell ◽  
Drosophila Embryo ◽  
Neuronal Precursors ◽  
Split Ends ◽  
Recognition Motifs ◽  
Midline Cells ◽  
Wrong Number ◽  
Nuclear Levels

split ends (spen) encodes nuclear 600 kDa proteins that contain RNA recognition motifs and a conserved C-terminal sequence. These features define a new protein family, Spen, which includes the vertebrate MINT transcriptional regulator. Zygotic spen mutants affect the growth and guidance of a subset of axons in the Drosophila embryo. Removing maternal and zygotic protein elicits cell-fate and more general axon-guidance defects that are not seen in zygotic mutants. The wrong number of chordotonal neurons and midline cells are generated, and we identify defects in precursor formation and EGF receptor-dependent inductive processes required for cell-fate specification. The number of neuronal precursors is variable in embryos that lack Spen. The levels of Suppressor of Hairless, a key transcriptional effector of Notch required for precursor formation, are reduced, as are the nuclear levels of Yan, a transcriptional repressor that regulates cell fate and proliferation downstream of the EGF receptor. We propose that Spen proteins regulate the expression of key effectors of signaling pathways required to specify neuronal cell fate and morphology.

scholarly journals Gene-free methodology for cell fate dynamics during development

eLife ◽  
2017 ◽  
Vol 6 ◽  
Author(s):  
Francis Corson ◽  
Eric D Siggia
Keyword(s):  
Cell Fate ◽  
Cell Function ◽  
Geometric Model ◽  
Model Fit ◽  
Vulval Development ◽  
Epistatic Interactions ◽  
Compact Representations ◽  
Special Points ◽  
Unexpected Outcomes

Models of cell function that assign a variable to each gene frequently lead to systems of equations with many parameters whose behavior is obscure. Geometric models reduce dynamics to intuitive pictorial elements that provide compact representations for sparse in vivo data and transparent descriptions of developmental transitions. To illustrate, a geometric model fit to vulval development in Caenorhabditis elegans, implies a phase diagram where cell-fate choices are displayed in a plane defined by EGF and Notch signaling levels. This diagram defines allowable and forbidden cell-fate transitions as EGF or Notch levels change, and explains surprising observations previously attributed to context-dependent action of these signals. The diagram also reveals the existence of special points at which minor changes in signal levels lead to strong epistatic interactions between EGF and Notch. Our model correctly predicts experiments near these points and suggests specific timed perturbations in signals that can lead to additional unexpected outcomes.

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.

scholarly journals Phase Transitioned Nuclear Oskar Promotes Cell Division of Drosophila Primordial Germ Cells

2018 ◽  
Author(s):  
Kathryn E. Kistler ◽  
Tatjana Trcek ◽  
Thomas R. Hurd ◽  
Ruoyu Chen ◽  
Feng-Xia Liang ◽  
...  
Keyword(s):  
Germ Cell ◽  
Cell Fate ◽  
Germ Cells ◽  
Cell Function ◽  
Primordial Germ Cells ◽  
Nuclear Localization Sequence ◽  
Cell Systems ◽  
Germ Granules ◽  
Localization Sequence ◽  
Transcriptional Gene Regulation

ABSTRACTGerm granules are non-membranous ribonucleoprotein granules deemed the hubs for post-transcriptional gene regulation and functionally linked to germ cell fate across species. Little is known about the physical properties of germ granules and how these relate to germ cell function. Here we study two types of germ granules in the Drosophila embryo: cytoplasmic germ granules that instruct primordial germ cells (PGCs) formation and nuclear germ granules within early PGCs with unknown function. We show that cytoplasmic and nuclear germ granules are phase transitioned condensates nucleated by Oskar protein that display liquid as well as hydrogel-like properties. Focusing on nuclear granules, we find that Oskar drives their formation in heterologous cell systems. Multiple, independent Oskar protein domains synergize to promote granule phase separation. Deletion of Oskar’s nuclear localization sequence specifically ablates nuclear granules in cell systems. In the embryo, nuclear germ granules promote germ cell divisions thereby increasing PGC number for the next generation.

scholarly journals Musashi-2 controls cell fate, lineage bias, and TGF-β signaling in HSCs

2014 ◽  
Vol 211 (1) ◽  
pp. 71-87 ◽  
Author(s):  
Sun-Mi Park ◽  
Raquel P. Deering ◽  
Yuheng Lu ◽  
Patrick Tivnan ◽  
Steve Lianoglou ◽  
...  
Keyword(s):  
Cell Fate ◽  
Rna Binding ◽  
Asymmetric Cell Division ◽  
Cell Function ◽  
Rna Binding Protein ◽  
Transcriptome Profiling ◽  
Hematopoietic Stem ◽  
Rna Translation ◽  
Important Regulator ◽  
Global Transcriptome

Hematopoietic stem cells (HSCs) are maintained through the regulation of symmetric and asymmetric cell division. We report that conditional ablation of the RNA-binding protein Msi2 results in a failure of HSC maintenance and engraftment caused by a loss of quiescence and increased commitment divisions. Contrary to previous studies, we found that these phenotypes were independent of Numb. Global transcriptome profiling and RNA target analysis uncovered Msi2 interactions at multiple nodes within pathways that govern RNA translation, stem cell function, and TGF-β signaling. Msi2-null HSCs are insensitive to TGF-β–mediated expansion and have decreased signaling output, resulting in a loss of myeloid-restricted HSCs and myeloid reconstitution. Thus, Msi2 is an important regulator of the HSC translatome and balances HSC homeostasis and lineage bias.

scholarly journals Placental, Matrilineal, and Epigenetic Mechanisms Promoting Environmentally Adaptive Development of the Mammalian Brain

2016 ◽  
Vol 2016 ◽  
pp. 1-8 ◽  
Author(s):  
Kevin D. Broad ◽  
Eridan Rocha-Ferreira ◽  
Mariya Hristova
Keyword(s):  
Genomic Imprinting ◽  
Neural Plasticity ◽  
Information Transfer ◽  
Developing Brain ◽  
Mammalian Brain ◽  
Neural Function ◽  
Mammalian Development ◽  
Intrauterine Development ◽  
Epigenetic Information ◽  
Ultimate Control

The evolution of intrauterine development, vivipary, and placentation in eutherian mammals has introduced new possibilities and constraints in the regulation of neural plasticity and development which promote neural function that is adaptive to the environment that a developing brain is likely to encounter in the future. A range of evolutionary adaptations associated with placentation transfers disproportionate control of this process to the matriline, a period unique in mammalian development in that there are three matrilineal genomes interacting in the same organism at the same time (maternal, foetal, and postmeiotic oocytes). The interactions between the maternal and developing foetal hypothalamus and placenta can provide a template by which a mother can transmit potentially adaptive information concerning potential future environmental conditions to the developing brain. In conjunction with genomic imprinting, it also provides a template to integrate epigenetic information from both maternal and paternal lineages. Placentation also hands ultimate control of genomic imprinting and intergenerational epigenetic information transfer to the matriline as epigenetic markers undergo erasure and reprogramming in the developing oocyte. These developments, in conjunction with an expanded neocortex, provide a unique evolutionary template by which matrilineal transfer of maternal care, resources, and culture can be used to promote brain development and infant survival.

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