Cell lineage in the developing neural tube

1998 ◽  
Vol 76 (6) ◽  
pp. 1051-1068 ◽  
Author(s):  
Anjali J Kalyani ◽  
Mahendra S Rao

Acquisition of cell type specific properties in the spinal cord is a process of sequential restriction in developmental potential. A multipotent stem cell of the nervous system, the neuroepithelial cell, generates central nervous system and peripheral nervous system derivatives via the generation of intermediate lineage restricted precursors that differ from each other and from neuroepithelial cells. Intermediate lineage restricted neuronal and glial precursors termed neuronal restricted precursors and glial restricted precursors, respectively, have been identified. Differentiation is influenced by extrinsic environmental signals that are stage and cell type specific. Analysis in multiple species illustrates similarities between chick, rat, mouse, and human cell differentiation. The utility of obtaining these precursor cell types for gene discovery, drug screening, and therapeutic applications is discussed.Key words: stem cells, oligodendrocytes, astrocytes, neurons, spinal cord.

2017 ◽  
Vol 2017 ◽  
pp. 1-8 ◽  
Author(s):  
Kathryn M. Madalena ◽  
Jessica K. Lerch

Stress, injury, and disease trigger glucocorticoid (GC) elevation. Elevated GCs bind to the ubiquitously expressed glucocorticoid receptor (GR). While GRs are in every cell in the nervous system, the expression level varies, suggesting that diverse cell types react differently to GR activation. Stress/GCs induce structural plasticity in neurons, Schwann cells, microglia, oligodendrocytes, and astrocytes as well as affect neurotransmission by changing the release and reuptake of glutamate. While general nervous system plasticity is essential for adaptation and learning and memory, stress-induced plasticity is often maladaptive and contributes to neuropsychiatric disorders and neuropathic pain. In this brief review, we describe the evidence that stress/GCs activate GR to promote cell type-specific changes in cellular plasticity throughout the nervous system.


2020 ◽  
Author(s):  
Manuela Wuelling ◽  
Christoph Neu ◽  
Andrea M. Thiesen ◽  
Simo Kitanovski ◽  
Yingying Cao ◽  
...  

AbstractEpigenetic modifications play critical roles in regulating cell lineage differentiation, but the epigenetic mechanisms guiding specific differentiation steps within a cell lineage have rarely been investigated. To decipher such mechanisms, we used the defined transition from proliferating (PC) into hypertrophic chondrocytes (HC) during endochondral ossification as a model. We established a map of activating and repressive histone modifications for each cell type. ChromHMM state transition analysis and Pareto-based integration of differential levels of mRNA and epigenetic marks revealed that differentiation associated gene repression is initiated by the addition of H3K27me3 to promoters still carrying substantial levels of activating marks. Moreover, the integrative analysis identified genes specifically expressed in cells undergoing the transition into hypertrophy.Investigation of enhancer profiles detected surprising differences in enhancer number, location, and transcription factor binding sites between the two closely related cell types. Furthermore, cell type-specific upregulation of gene expression was associated with a shift from low to high H3K27ac decoration. Pathway analysis identified PC-specific enhancers associated with chondrogenic genes, while HC-specific enhancers mainly control metabolic pathways linking epigenetic signature to biological functions.


1990 ◽  
Vol 111 (1) ◽  
pp. 209-215 ◽  
Author(s):  
A da Cunha ◽  
L Vitković

Growth-associated protein 43 (GAP-43) is an abundant, intensely investigated membrane phosphoprotein of the nervous system (Benowitz, L.I., and A. Routtenberg. 1987. Trends Neurosci. 10:527-532; Skene, J. H. P. 1989. Annu. Rev. Neurosci. 12:127-156), with a hitherto unknown function. We have previously demonstrated that astrocytes, brain macroglial cells, contain GAP-43 (Steisslinger, H. W., V. J. Aloyo, and L. Vitković, 1987. Brain Res. 415:375-379; Vitković, L., H. W. Steisslinger, V. J. Aloyo, and M. Mersel. 1988. Proc. Natl. Acad. Sci. USA. 85:8296-8300; Vitković L., and M. Mersel. 1989. Metab. Brain Dis. 4:47-53). Results from double immunofluorescent labeling experiments presented here show that oligodendrocytes also contain GAP-43 immunoreactivity (GAP-43ir). Thus, all three macroglial cell types of the central nervous system (type I and type 2 astrocytes and oligodendrocytes) contain GAP-43. Whereas immunoreactive GAP-43 is expressed by progenitors of all macroglial cell types, the developmental regulation of its expression is cell type specific. Immunoreactive GAP-43 is downregulated in type 1 astrocytes, and constitutively expressed in both type 2 astrocytes and oligodendrocytes. These results may be relevant to potential function(s) of GAP-43.


2021 ◽  
Vol 118 (8) ◽  
pp. e2011491118 ◽  
Author(s):  
Ekin Bolukbasi ◽  
Nathaniel S. Woodling ◽  
Dobril K. Ivanov ◽  
Jennifer Adcott ◽  
Andrea Foley ◽  
...  

Reduced activity of insulin/insulin-like growth factor signaling (IIS) increases healthy lifespan among diverse animal species. Downstream of IIS, multiple evolutionarily conserved transcription factors (TFs) are required; however, distinct TFs are likely responsible for these effects in different tissues. Here we have asked which TFs can extend healthy lifespan within distinct cell types of the adult nervous system in Drosophila. Starting from published single-cell transcriptomic data, we report that forkhead (FKH) is endogenously expressed in neurons, whereas forkhead-box-O (FOXO) is expressed in glial cells. Accordingly, we find that neuronal FKH and glial FOXO exert independent prolongevity effects. We have further explored the role of neuronal FKH in a model of Alzheimer’s disease-associated neuronal dysfunction, where we find that increased neuronal FKH preserves behavioral function and reduces ubiquitinated protein aggregation. Finally, using transcriptomic profiling, we identify Atg17, a member of the Atg1 autophagy initiation family, as one FKH-dependent target whose neuronal overexpression is sufficient to extend healthy lifespan. Taken together, our results underscore the importance of cell type-specific mapping of TF activity to preserve healthy function with age.


2016 ◽  
Author(s):  
B. Ogan Mancarci ◽  
Lilah Toker ◽  
Shreejoy J Tripathy ◽  
Brenna Li ◽  
Brad Rocco ◽  
...  

AbstractEstablishing the molecular diversity of cell types is crucial for the study of the nervous system. We compiled a cross-laboratory database of mouse brain cell type-specific transcriptomes from 36 major cell types from across the mammalian brain using rigorously curated published data from pooled cell type microarray and single cell RNA-sequencing studies. We used these data to identify cell type-specific marker genes, discovering a substantial number of novel markers, many of which we validated using computational and experimental approaches. We further demonstrate that summarized expression of marker gene sets in bulk tissue data can be used to estimate the relative cell type abundance across samples. To facilitate use of this expanding resource, we provide a user-friendly web interface at Neuroexpresso.org.Significance StatementCell type markers are powerful tools in the study of the nervous system that help reveal properties of cell types and acquire additional information from large scale expression experiments. Despite their usefulness in the field, known marker genes for brain cell types are few in number. We present NeuroExpresso, a database of brain cell type specific gene expression profiles, and demonstrate the use of marker genes for acquiring cell type specific information from whole tissue expression. The database will prove itself as a useful resource for researchers aiming to reveal novel properties of the cell types and aid both laboratory and computational scientists to unravel the cell type specific components of brain disorders.


2021 ◽  
Vol 55 (1) ◽  
Author(s):  
Shashank Gandhi ◽  
Marianne E. Bronner

Neural crest stem/progenitor cells arise early during vertebrate embryogenesis at the border of the forming central nervous system. They subsequently migrate throughout the body, eventually differentiating into diverse cell types ranging from neurons and glia of the peripheral nervous system to bones of the face, portions of the heart, and pigmentation of the skin. Along the body axis, the neural crest is heterogeneous, with different subpopulations arising in the head, neck, trunk, and tail regions, each characterized by distinct migratory patterns and developmental potential. Modern genomic approaches like single-cell RNA- and ATAC-sequencing (seq) have greatly enhanced our understanding of cell lineage trajectories and gene regulatory circuitry underlying the developmental progression of neural crest cells. Here, we discuss how genomic approaches have provided new insights into old questions in neural crest biology by elucidating transcriptional and posttranscriptional mechanisms that govern neural crest formation and the establishment of axial level identity. Expected final online publication date for the Annual Review of Genetics, Volume 55 is November 2021. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.


2018 ◽  
Author(s):  
Jun Ding ◽  
Chieh Lin ◽  
Ziv Bar-Joseph

Several recent studies focus on the inference of developmental and response trajectories from single cell NA-Seq (scRNA-Seq) data. A number of computational methods, often referred to as pseudo-time ordering, have been developed for this task. Recently, CRISPR has also been used to reconstruct lineage trees by inserting random mutations. However, both approaches suffer from drawbacks that limit their use. Here we develop a method to detect significant, cell type specific, sequence mutations from scRNA-Seq data. We show that only a few mutations are enough for reconstructing good branching models. Integrating these mutations with expression data further improves the accuracy of the reconstructed models. As we show, the majority of mutations we identify are likely RNA editing events indicating that such information can be used to distinguish cell types.


2018 ◽  
Author(s):  
Yuan Yuan ◽  
Shirley Xie ◽  
Jennifer C. Darnell ◽  
Andrew J. Darnell ◽  
Yuhki Saito ◽  
...  

AbstractBackgroundAlternative RNA processing plays an essential role in shaping cell identity and connectivity in the central nervous system (CNS). This is believed to involve differential regulation of RNA processing in various cell types. However, in vivo study of cell-type specific post-transcriptional regulation has been a challenge. Here, we developed a sensitive and stringent method combining genetics and CLIP (crosslinking and immunoprecipitation) to globally identify regulatory interactions between NOVA and RNA in the mouse spinal cord motoneurons (MNs).ResultsWe developed a means of undertaking MN-specific CLIP to explore MN-specific protein-RNA interactions relative to studies of the whole spinal cord. This allowed us to pinpoint differential RNA regulation specific to MNs, revealing major role for NOVA in regulating cytoskeleton interactions in MNs. In particular, NOVA specifically promotes the palmitoylated isoform of a cytoskeleton protein Septin 8 in MNs, which enhances dendritic arborization.ConclusionsOur study demonstrates that cell type-specific RNA regulation is important for fine-tuning motoneuron physiology, and highlights the value of defining RNA processing regulation at single cell type resolution.


2018 ◽  
Author(s):  
Alexandra L. McCorkindale ◽  
Philipp Wahle ◽  
Sascha Werner ◽  
Irwin Jungreis ◽  
Peter Menzel ◽  
...  

Summary statementWe present a spatiotemporal transcriptome during early Drosophila embryonic nervous system development, revealing a complex cell type-specific network of mRNAs and lncRNAs.AbstractCell type specification during early nervous system development in Drosophila melanogaster requires precise regulation of gene expression in time and space. Resolving the programs driving neurogenesis has been a major challenge owing to the complexity and rapidity with which distinct cell populations arise. To resolve the cell type-specific gene expression dynamics in early nervous system development, we have sequenced the transcriptomes of purified neurogenic cell types across consecutive time points covering critical events in neurogenesis. The resulting gene expression atlas comprises a detailed resource of global transcriptome dynamics that permits systematic analysis of how cells in the nervous system acquire distinct fates. We resolve known gene expression dynamics and uncover novel expression signatures for hundreds of genes among diverse neurogenic cell types, most of which remain unstudied. We also identified a set of conserved and tissue-specifically regulated long-noncoding RNAs (lncRNAs) that exhibit spatiotemporal expression during neurogenesis with exquisite specificity. LncRNA expression is highly dynamic and demarcates specific subpopulations within neurogenic cell types. Our spatiotemporal transcriptome atlas provides a comprehensive resource to investigate the function of coding genes and noncoding RNAs during critical stages of early neurogenesis.


2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Houri Hintiryan ◽  
Ian Bowman ◽  
David L. Johnson ◽  
Laura Korobkova ◽  
Muye Zhu ◽  
...  

AbstractThe basolateral amygdalar complex (BLA) is implicated in behaviors ranging from fear acquisition to addiction. Optogenetic methods have enabled the association of circuit-specific functions to uniquely connected BLA cell types. Thus, a systematic and detailed connectivity profile of BLA projection neurons to inform granular, cell type-specific interrogations is warranted. Here, we apply machine-learning based computational and informatics analysis techniques to the results of circuit-tracing experiments to create a foundational, comprehensive BLA connectivity map. The analyses identify three distinct domains within the anterior BLA (BLAa) that house target-specific projection neurons with distinguishable morphological features. We identify brain-wide targets of projection neurons in the three BLAa domains, as well as in the posterior BLA, ventral BLA, posterior basomedial, and lateral amygdalar nuclei. Inputs to each nucleus also are identified via retrograde tracing. The data suggests that connectionally unique, domain-specific BLAa neurons are associated with distinct behavior networks.


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