scholarly journals Cerebral Organoids—Challenges to Establish a Brain Prototype

Cells ◽  
2021 ◽  
Vol 10 (7) ◽  
pp. 1790
Author(s):  
Artem V. Eremeev ◽  
Olga S. Lebedeva ◽  
Margarita E. Bogomiakova ◽  
Maria A. Lagarkova ◽  
Alexandra N. Bogomazova
Keyword(s):  
Nervous System ◽  
Brain Tissue ◽  
System Development ◽  
Cell Types ◽  
Nervous System Development ◽  
Neural Cells ◽  
Human Brain Tissue ◽  
Cellular Models ◽  
Stage Of Development ◽  
Pharmacologically Active

The new cellular models based on neural cells differentiated from induced pluripotent stem cells have greatly enhanced our understanding of human nervous system development. Highly efficient protocols for the differentiation of iPSCs into different types of neural cells have allowed the creation of 2D models of many neurodegenerative diseases and nervous system development. However, the 2D culture of neurons is an imperfect model of the 3D brain tissue architecture represented by many functionally active cell types. The development of protocols for the differentiation of iPSCs into 3D cerebral organoids made it possible to establish a cellular model closest to native human brain tissue. Cerebral organoids are equally suitable for modeling various CNS pathologies, testing pharmacologically active substances, and utilization in regenerative medicine. Meanwhile, this technology is still at the initial stage of development.

scholarly journals A Comprehensive Review: Sphingolipid Metabolism and Implications of Disruption in Sphingolipid Homeostasis

2021 ◽  
Vol 22 (11) ◽  
pp. 5793
Author(s):  
Brianna M. Quinville ◽  
Natalie M. Deschenes ◽  
Alex E. Ryckman ◽  
Jagdeep S. Walia
Keyword(s):  
Nervous System ◽  
Large Scale ◽  
System Development ◽  
Building Blocks ◽  
Cell Types ◽  
Nervous System Development ◽  
Sphingolipid Metabolism ◽  
Lysosomal Storage ◽  
Bioactive Lipids ◽  
Comprehensive Review

Sphingolipids are a specialized group of lipids essential to the composition of the plasma membrane of many cell types; however, they are primarily localized within the nervous system. The amphipathic properties of sphingolipids enable their participation in a variety of intricate metabolic pathways. Sphingoid bases are the building blocks for all sphingolipid derivatives, comprising a complex class of lipids. The biosynthesis and catabolism of these lipids play an integral role in small- and large-scale body functions, including participation in membrane domains and signalling; cell proliferation, death, migration, and invasiveness; inflammation; and central nervous system development. Recently, sphingolipids have become the focus of several fields of research in the medical and biological sciences, as these bioactive lipids have been identified as potent signalling and messenger molecules. Sphingolipids are now being exploited as therapeutic targets for several pathologies. Here we present a comprehensive review of the structure and metabolism of sphingolipids and their many functional roles within the cell. In addition, we highlight the role of sphingolipids in several pathologies, including inflammatory disease, cystic fibrosis, cancer, Alzheimer’s and Parkinson’s disease, and lysosomal storage disorders.

Spalt modifies EGFR-mediated induction of chordotonal precursors in the embryonic PNS of Drosophila promoting the development of oenocytes

Development ◽  
2001 ◽  
Vol 128 (5) ◽  
pp. 711-722 ◽  
Author(s):  
T.E. Rusten ◽  
R. Cantera ◽  
J. Urban ◽  
G. Technau ◽  
F.C. Kafatos ◽  
...  
Keyword(s):  
Nervous System ◽  
Cell Fate ◽  
System Development ◽  
Cell Types ◽  
Nervous System Development ◽  
Dual Function ◽  
Evolutionarily Conserved ◽  
A Cell ◽  
And Migration

Genes of the spalt family encode nuclear zinc finger proteins. In Drosophila melanogaster, they are necessary for the establishment of head/trunk identity, correct tracheal migration and patterning of the wing imaginal disc. Spalt proteins display a predominant pattern of expression in the nervous system, not only in Drosophila but also in species of fish, mouse, frog and human, suggesting an evolutionarily conserved role for these proteins in nervous system development. Here we show that Spalt works as a cell fate switch between two EGFR-induced cell types, the oenocytes and the precursors of the pentascolopodial organ in the embryonic peripheral nervous system. We show that removal of spalt increases the number of scolopodia, as a result of extra secondary recruitment of precursor cells at the expense of the oenocytes. In addition, the absence of spalt causes defects in the normal migration of the pentascolopodial organ. The dual function of spalt in the development of this organ, recruitment of precursors and migration, is reminiscent of its role in tracheal formation and of the role of a spalt homologue, sem-4, in the Caenorhabditis elegans nervous system.

scholarly journals Differing strategies used by motor neurons and glia to achieve robust development of an adult neuropil in Drosophila

2017 ◽  
Author(s):  
Jonathan Enriquez ◽  
Laura Quintana Rio ◽  
Richard Blazeski ◽  
Carol Mason ◽  
Richard S. Mann
Keyword(s):  
Stem Cells ◽  
Nervous System ◽  
Birth Order ◽  
Motor Neurons ◽  
Neural Circuits ◽  
System Development ◽  
Cell Types ◽  
Nervous System Development ◽  
Factor Code ◽  
Individual Motor

SummaryIn both vertebrates and invertebrates, neurons and glia are generated in a stereotyped order from dedicated progenitors called neural stem cells, but the purpose of invariant lineages is not understood. Here we show that three of the stem cells that produce leg motor neurons in Drosophila also generate a specialized subset of glia, the neuropil glia, which wrap and send processes into the neuropil where motor neuron dendrites arborize. The development of the neuropil glia and leg motor neurons is highly coordinated. However, although individual motor neurons have a stereotyped birth order and transcription factor code, both the number and individual morphologies of the glia born from these lineages are highly plastic, even though the final structure they contribute to is highly stereotyped. We suggest that the shared lineages of these two cell types facilitates the assembly of complex neural circuits, and that the two different birth order strategies – hardwired for motor neurons and flexible for glia – are important for robust nervous system development and homeostasis.

scholarly journals Single-Cell Multiomic Approaches Reveal Diverse Labeling of the Nervous System by Common Cre-Drivers

2021 ◽  
Vol 15 ◽  
Author(s):  
Rachel A. Keuls ◽  
Ronald J. Parchem
Keyword(s):  
Nervous System ◽  
Neural Crest ◽  
Single Cell ◽  
System Development ◽  
Cell Types ◽  
Nervous System Development ◽  
Cellular Heterogeneity ◽  
Cranial Neural Crest ◽  
Developmental Potential ◽  
Neural Crest Development

Neural crest development involves a series of dynamic, carefully coordinated events that result in human disease when not properly orchestrated. Cranial neural crest cells acquire unique multipotent developmental potential upon specification to generate a broad variety of cell types. Studies of early mammalian neural crest and nervous system development often use the Cre-loxP system to lineage trace and mark cells for further investigation. Here, we carefully profile the activity of two common neural crest Cre-drivers at the end of neurulation in mice. RNA sequencing of labeled cells at E9.5 reveals that Wnt1-Cre2 marks cells with neuronal characteristics consistent with neuroepithelial expression, whereas Sox10-Cre predominantly labels the migratory neural crest. We used single-cell mRNA and single-cell ATAC sequencing to profile the expression of Wnt1 and Sox10 and identify transcription factors that may regulate the expression of Wnt1-Cre2 in the neuroepithelium and Sox10-Cre in the migratory neural crest. Our data identify cellular heterogeneity during cranial neural crest development and identify specific populations labeled by two Cre-drivers in the developing nervous system.

Role of leukemia inhibitory factor in the nervous system and its pathology

2015 ◽  
Vol 26 (4) ◽  
Author(s):  
Pavel Ostasov ◽  
Zbynek Houdek ◽  
Jan Cendelin ◽  
Milena Kralickova
Keyword(s):  
Nervous System ◽  
Signaling Pathway ◽  
Leukemia Inhibitory Factor ◽  
System Development ◽  
Cell Types ◽  
Nervous System Development ◽  
Inhibitory Factor ◽  
Therapeutic Interventions ◽  
Brain Diseases ◽  
And Function

AbstractLeukemia inhibitory factor (LIF) is a multifunction cytokine that has various effects on different tissues and cell types in rodents and humans; however, its insufficiency has a relatively mild impact. This could explain why only some aspects of LIF activity are in the limelight, whereas other aspects are not well known. In this review, the LIF structure, signaling pathway, and primary roles in the development and function of an organism are reviewed, and the effects of LIF on stem cell growth and differentiation, which are important for its use in cell culturing, are described. The focus is on the roles of LIF in central nervous system development and on the modulation of its physiological functions as well as the involvement of LIF in the pathogenesis of brain diseases and injuries. Finally, LIF and its signaling pathway are discussed as potential targets of therapeutic interventions to influence both negative phenomena and regenerative processes following brain injury.

Neurons from stem cells: Implications for understanding nervous system development and repair

2000 ◽  
Vol 78 (5) ◽  
pp. 613-628 ◽  
Author(s):  
Fiona C Mansergh ◽  
Michael A Wride ◽  
Derrick E Rancourt
Keyword(s):  
Stem Cells ◽  
Nervous System ◽  
Neural Differentiation ◽  
System Development ◽  
Nervous System Development ◽  
Neural Cells ◽  
Ageing Population ◽  
Bioinformatic Tools ◽  
Functional Characterisation

Neurodegenerative diseases cost the economies of the developed world billions of dollars per annum. Given ageing population profiles and the increasing extent of this problem, there has been a surge of interest in neural stem cells and in neural differentiation protocols that yield neural cells for therapeutic transplantation. Due to the oncogenic potential of stem cells a better characterisation of neural differentiation, including the identification of new neurotrophic factors, is required. Stem cell cultures undergoing synchronous in vitro neural differentiation provide a valuable resource for gene discovery. Novel tools such as microarrays promise to yield information regarding gene expression in stem cells. With the completion of the yeast, C. elegans, Drosophila, human, and mouse genome projects, the functional characterisation of genes using genetic and bioinformatic tools will aid in the identification of important regulators of neural differentiation.Key words: neural differentiation, neural precursor cell, brain repair, central nervous system repair, CNS.

Involvement of the guanine nucleotide exchange factor Vav3 in central nervous system development and plasticity

2017 ◽  
Vol 398 (5-6) ◽  
pp. 663-675 ◽  
Author(s):  
Annika Ulc ◽  
Christine Gottschling ◽  
Ina Schäfer ◽  
David Wegrzyn ◽  
Simon van Leeuwen ◽  
...  
Keyword(s):  
Nervous System ◽  
Cell Biology ◽  
System Development ◽  
Cell Types ◽  
Nervous System Development ◽  
Guanine Nucleotide ◽  
Nucleotide Exchange ◽  
Guanine Nucleotide Exchange ◽  
Nucleotide Exchange Factor ◽  
Hydrolyzing Enzymes

Abstract Small GTP-hydrolyzing enzymes (GTPases) of the RhoA family play manifold roles in cell biology and are regulated by upstream guanine nucleotide exchange factors (GEFs). Herein, we focus on the GEFs of the Vav subfamily. Vav1 was originally described as a proto-oncogene of the hematopoietic lineage. The GEFs Vav2 and Vav3 are more broadly expressed in various tissues. In particular, the GEF Vav3 may play important roles in the developing nervous system during the differentiation of neural stem cells into the major lineages, namely neurons, oligodendrocytes and astrocytes. We discuss its putative regulatory roles for progenitor differentiation in the developing retina, polarization of neurons and formation of synapses, migration of oligodendrocyte progenitors and establishment of myelin sheaths. We propose that Vav3 mediates the response of various neural cell types to environmental cues.

scholarly journals SOX Transcription Factors as Important Regulators of Neuronal and Glial Differentiation During Nervous System Development and Adult Neurogenesis

2021 ◽  
Vol 14 ◽  
Author(s):  
Milena Stevanovic ◽  
Danijela Drakulic ◽  
Andrijana Lazic ◽  
Danijela Stanisavljevic Ninkovic ◽  
Marija Schwirtlich ◽  
...  
Keyword(s):  
Nervous System ◽  
Transcription Factors ◽  
Adult Neurogenesis ◽  
Current Knowledge ◽  
System Development ◽  
Nervous System Development ◽  
Glial Differentiation ◽  
Neural Lineage ◽  
Stage Of Development ◽  
Sox Proteins

The SOX proteins belong to the superfamily of transcription factors (TFs) that display properties of both classical TFs and architectural components of chromatin. Since the cloning of the Sox/SOX genes, remarkable progress has been made in illuminating their roles as key players in the regulation of multiple developmental and physiological processes. SOX TFs govern diverse cellular processes during development, such as maintaining the pluripotency of stem cells, cell proliferation, cell fate decisions/germ layer formation as well as terminal cell differentiation into tissues and organs. However, their roles are not limited to development since SOX proteins influence survival, regeneration, cell death and control homeostasis in adult tissues. This review summarized current knowledge of the roles of SOX proteins in control of central nervous system development. Some SOX TFs suspend neural progenitors in proliferative, stem-like state and prevent their differentiation. SOX proteins function as pioneer factors that occupy silenced target genes and keep them in a poised state for activation at subsequent stages of differentiation. At appropriate stage of development, SOX members that maintain stemness are down-regulated in cells that are competent to differentiate, while other SOX members take over their functions and govern the process of differentiation. Distinct SOX members determine down-stream processes of neuronal and glial differentiation. Thus, sequentially acting SOX TFs orchestrate neural lineage development defining neuronal and glial phenotypes. In line with their crucial roles in the nervous system development, deregulation of specific SOX proteins activities is associated with neurodevelopmental disorders (NDDs). The overview of the current knowledge about the link between SOX gene variants and NDDs is presented. We outline the roles of SOX TFs in adult neurogenesis and brain homeostasis and discuss whether impaired adult neurogenesis, detected in neurodegenerative diseases, could be associated with deregulation of SOX proteins activities. We present the current data regarding the interaction between SOX proteins and signaling pathways and microRNAs that play roles in nervous system development. Finally, future research directions that will improve the knowledge about distinct and various roles of SOX TFs in health and diseases are presented and discussed.

Signaling in glial development: differentiation migration and axon guidance

2004 ◽  
Vol 82 (6) ◽  
pp. 694-707 ◽  
Author(s):  
Robert J Parker ◽  
Vanessa J Auld
Keyword(s):  
Nervous System ◽  
Axon Guidance ◽  
Egf Receptor ◽  
System Development ◽  
Molecular Genetic ◽  
Model Organism ◽  
Cell Types ◽  
Nervous System Development ◽  
Glial Development ◽  
Embryonic Nervous System

Glial cells have diverse functions that are necessary for the proper development and function of complex nervous systems. During development, a variety of reciprocal signaling interactions between glia and neurons dictate all parts of nervous system development. Glia may provide attractive, repulsive, or contact-mediated cues to steer neuronal growth cones and ensure that neurons find their appropriate synaptic targets. In fact, both neurons and glia may act as migrational substrates for one another at different times during development. Also, the exchange of trophic signals between glia and neurons is essential for the proper bundling, fasciculation, and ensheathement of axons as well as the differentiation and survival of both cell types. The growing number of links between glial malfunction and human disease has generated great interest in glial biology. Because of its relative simplicity and the many molecular genetic tools available, Drosophila is an excellent model organism for studying glial development. This review will outline the roles of glia and their interactions with neurons in the embryonic nervous system of the fly.Key words: glia, axon guidance, migration, EGF receptor.

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