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

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.

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

International Journal of Molecular Sciences ◽

10.3390/ijms22115793 ◽

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.

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News from the endothelin-3/EDNRB signaling pathway: Role during enteric nervous system development and involvement in neural crest-associated disorders

Developmental Biology ◽

10.1016/j.ydbio.2018.08.014 ◽

2018 ◽

Vol 444 ◽

pp. S156-S169 ◽

Cited By ~ 8

Author(s):

Nadege Bondurand ◽

Sylvie Dufour ◽

Veronique Pingault

Keyword(s):

Nervous System ◽

Neural Crest ◽

Enteric Nervous System ◽

Signaling Pathway ◽

System Development ◽

Nervous System Development ◽

Endothelin 3 ◽

Enteric Nervous System Development

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

Development ◽

10.1242/dev.128.5.711 ◽

2001 ◽

Vol 128 (5) ◽

pp. 711-722 ◽

Cited By ~ 3

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.

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Vitamin E is Necessary to Protect Neural Crest Cells in Developing Zebrafish Embryos

Current Developments in Nutrition ◽

10.1093/cdn/nzaa057_025 ◽

2020 ◽

Vol 4 (Supplement_2) ◽

pp. 1209-1209

Author(s):

Brian Head ◽

Jane La Du ◽

Robyn Tanguay ◽

Chrissa Kioussi ◽

Maret Traber

Keyword(s):

Nervous System ◽

Vitamin E ◽

Neural Crest ◽

System Development ◽

Neural Crest Cells ◽

Nervous System Development ◽

Neural Plate ◽

Zebrafish Embryos ◽

Normal Brain ◽

Collagen Formation

Abstract Objectives Vitamin E (VitE) deficiency causes vertebrate embryonic lethality. The alpha-tocopherol transfer protein (Ttpa) likely regulates VitE distribution in the early zebrafish embryo because Ttpa knockdown causes impaired nervous system development and embryonic death by 15–18 hours post-fertilization (hpf). We propose that VitE is necessary for normal brain and peripheral nervous system development. Methods Zebrafish embryos are obtained from adults fed either VitE sufficient (E+) or deficient (E–) diets for at least 80 days. Embryos at 12 and 24 hpf are subjected to RNA whole mount in situ hybridization (WISH). RNA is also collected from embryos at 12, 18 and 24 hpf for RT-qPCR of specific targets. Results At 12 hpf, the midbrain-hindbrain boundary and otic placodes are malformed in E– embryos, as shown by Pax2a expression. Similarly, Sox10 expression shows that E– embryos lack clear neural plate borders. Nonetheless, in 12 hpf E + and E− embryos Ttpa is localized similarly throughout the nervous system. Pax2a expression initiates collagen formation in the developing notochord. Collagen genes, col2a1a and col9a2, expression patterns showed abnormal notochord structures in 24 hpf E– embryos. At 24 hpf in E + embryos, Sox10 expressing-neural crest cells are localized both in the central nervous system and dorsal root ganglia (DRG), while the Sox10 signal is diminished in E– embryos in both the DRG and early enteric nervous system. At 24 hpf, Ttpa expression outlines the brain ventricle borders; critically E– embryos show reduced Ttpa signal and impaired ventricle closing. Gene expression by qPCR will be used to confirm these results. Conclusions This VitE deficient embryo model suggests that the carefully programmed development of the nervous system is distorted due to lack of adequate VitE. Thus, Ttpa and VitE are critical molecules for neural plate and neural tube formation, and neural crest cell migration. Funding Sources The authors received no specific funding for this work.

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

10.1101/149229 ◽

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.

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Enteric nervous system development: migration, differentiation, and disease

AJP Gastrointestinal and Liver Physiology ◽

10.1152/ajpgi.00452.2012 ◽

2013 ◽

Vol 305 (1) ◽

pp. G1-G24 ◽

Cited By ~ 161

Author(s):

Jonathan I. Lake ◽

Robert O. Heuckeroth

Keyword(s):

Nervous System ◽

Neural Crest ◽

Enteric Nervous System ◽

System Development ◽

Hirschsprung Disease ◽

Nervous System Development ◽

Receptor Type ◽

Model Organisms ◽

Endothelin Receptor ◽

Type B

The enteric nervous system (ENS) provides the intrinsic innervation of the bowel and is the most neurochemically diverse branch of the peripheral nervous system, consisting of two layers of ganglia and fibers encircling the gastrointestinal tract. The ENS is vital for life and is capable of autonomous regulation of motility and secretion. Developmental studies in model organisms and genetic studies of the most common congenital disease of the ENS, Hirschsprung disease, have provided a detailed understanding of ENS development. The ENS originates in the neural crest, mostly from the vagal levels of the neuraxis, which invades, proliferates, and migrates within the intestinal wall until the entire bowel is colonized with enteric neural crest-derived cells (ENCDCs). After initial migration, the ENS develops further by responding to guidance factors and morphogens that pattern the bowel concentrically, differentiating into glia and neuronal subtypes and wiring together to form a functional nervous system. Molecules controlling this process, including glial cell line-derived neurotrophic factor and its receptor RET, endothelin (ET)-3 and its receptor endothelin receptor type B, and transcription factors such as SOX10 and PHOX2B, are required for ENS development in humans. Important areas of active investigation include mechanisms that guide ENCDC migration, the role and signals downstream of endothelin receptor type B, and control of differentiation, neurochemical coding, and axonal targeting. Recent work also focuses on disease treatment by exploring the natural role of ENS stem cells and investigating potential therapeutic uses. Disease prevention may also be possible by modifying the fetal microenvironment to reduce the penetrance of Hirschsprung disease-causing mutations.

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

Reviews in the Neurosciences ◽

10.1515/revneuro-2014-0086 ◽

2015 ◽

Vol 26 (4) ◽

Cited By ~ 6

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.

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