scholarly journals GABAergic Neuron Specification in the Spinal Cord, the Cerebellum, and the Cochlear Nucleus

2012 ◽  
Vol 2012 ◽  
pp. 1-11 ◽  
Author(s):  
Kei Hori ◽  
Mikio Hoshino
Keyword(s):  
Spinal Cord ◽  
Nervous System ◽  
Cochlear Nucleus ◽  
Neuronal Cell ◽  
Cell Types ◽  
Brain Regions ◽  
Lineage Tracing ◽  
Inhibitory Neurons ◽  
Genetic Lineage ◽  
Genetic Lineage Tracing

In the nervous system, there are a wide variety of neuronal cell types that have morphologically, physiologically, and histochemically different characteristics. These various types of neurons can be classified into two groups: excitatory and inhibitory neurons. The elaborate balance of the activities of the two types is very important to elicit higher brain function, because its imbalance may cause neurological disorders, such as epilepsy and hyperalgesia. In the central nervous system, inhibitory neurons are mainly represented by GABAergic ones with some exceptions such as glycinergic. Although the machinery to specify GABAergic neurons was first studied in the telencephalon, identification of key molecules, such as pancreatic transcription factor 1a (Ptf1a), as well as recently developed genetic lineage-tracing methods led to the better understanding of GABAergic specification in other brain regions, such as the spinal cord, the cerebellum, and the cochlear nucleus.

scholarly journals Prevalent presence of periodic actin–spectrin-based membrane skeleton in a broad range of neuronal cell types and animal species

2016 ◽  
Vol 113 (21) ◽  
pp. 6029-6034 ◽  
Author(s):  
Jiang He ◽  
Ruobo Zhou ◽  
Zhuhao Wu ◽  
Monica A. Carrasco ◽  
Peri T. Kurshan ◽  
...  
Keyword(s):  
Glial Cell ◽  
Animal Species ◽  
Homo Sapiens ◽  
Neuronal Cell ◽  
Cell Types ◽  
Membrane Skeleton ◽  
Brain Regions ◽  
Inhibitory Neurons ◽  
Periodic Distribution ◽  
Neuronal Types

Actin, spectrin, and associated molecules form a periodic, submembrane cytoskeleton in the axons of neurons. For a better understanding of this membrane-associated periodic skeleton (MPS), it is important to address how prevalent this structure is in different neuronal types, different subcellular compartments, and across different animal species. Here, we investigated the organization of spectrin in a variety of neuronal- and glial-cell types. We observed the presence of MPS in all of the tested neuronal types cultured from mouse central and peripheral nervous systems, including excitatory and inhibitory neurons from several brain regions, as well as sensory and motor neurons. Quantitative analyses show that MPS is preferentially formed in axons in all neuronal types tested here: Spectrin shows a long-range, periodic distribution throughout all axons but appears periodic only in a small fraction of dendrites, typically in the form of isolated patches in subregions of these dendrites. As in dendrites, we also observed patches of periodic spectrin structures in a small fraction of glial-cell processes in four types of glial cells cultured from rodent tissues. Interestingly, despite its strong presence in the axonal shaft, MPS is disrupted in most presynaptic boutons but is present in an appreciable fraction of dendritic spine necks, including some projecting from dendrites where such a periodic structure is not observed in the shaft. Finally, we found that spectrin is capable of adopting a similar periodic organization in neurons of a variety of animal species, including Caenorhabditis elegans, Drosophila, Gallus gallus, Mus musculus, and Homo sapiens.

scholarly journals Single-nuclei transcriptomics of schizophrenia prefrontal cortex primarily implicates neuronal subtypes

2020 ◽  
Author(s):  
Benjamin C. Reiner ◽  
Richard C. Crist ◽  
Lauren M. Stein ◽  
Andrew E. Weller ◽  
Glenn A. Doyle ◽  
...  
Keyword(s):  
Prefrontal Cortex ◽  
Differentially Expressed Genes ◽  
Neuronal Cell ◽  
Cell Types ◽  
Brain Regions ◽  
Differentially Expressed ◽  
Inhibitory Neurons ◽  
Specific Cell ◽  
Dorsolateral Prefrontal ◽  
Layer V

AbstractTranscriptomic studies of bulk neural tissue homogenates from persons with schizophrenia and controls have identified differentially expressed genes in multiple brain regions. However, the heterogeneous nature prevents identification of relevant cell types. This study analyzed single-nuclei transcriptomics of ∼311,000 nuclei from frozen human postmortem dorsolateral prefrontal cortex samples from individuals with schizophrenia (n = 14) and controls (n = 16). 2,846 differential expression events were identified in 2,195 unique genes in 19 of 24 transcriptomically-distinct cell populations. ∼97% of differentially expressed genes occurred in five neuronal cell types, with ∼63% occurring in a subtype of PVALB+ inhibitory neurons and HTR2C+ layer V excitatory neurons. Differentially expressed genes were enriched for genes localized to schizophrenia GWAS loci. Cluster-specific changes in canonical pathways, upstream regulators and causal networks were identified. These results expand our knowledge of disrupted gene expression in specific cell types and permit new insight into the pathophysiology of schizophrenia.

scholarly journals Cellular origins and lineage relationships of the intestinal epithelium

2021 ◽  
Author(s):  
Claudia Capdevila ◽  
Maria Trifas ◽  
Jonathan Miller ◽  
Troy Anderson ◽  
Peter A. Sims ◽  
...  
Keyword(s):  
Intestinal Epithelium ◽  
Developmental Trajectories ◽  
Cell Lineage ◽  
Cell Types ◽  
Lineage Tracing ◽  
Hierarchical Organization ◽  
Genetic Lineage ◽  
Intestinal Epithelial ◽  
Lineage Specification ◽  
Genetic Lineage Tracing

Knowledge of the development and hierarchical organization of tissues is key to understanding how they are perturbed in injury and disease, as well as how they may be therapeutically manipulated to restore homeostasis. The rapidly regenerating intestinal epithelium harbors diverse cell types and their lineage relationships have been studied using numerous approaches, from classical label-retaining and genetic lineage tracing methods to novel transcriptome-based annotations. Here, we describe the developmental trajectories that dictate differentiation and lineage specification in the intestinal epithelium. We focus on the most recent single-cell RNA-sequencing (scRNA-seq)-based strategies for understanding intestinal epithelial cell lineage relationships, underscoring how they have refined our view of the development of this tissue and highlighting their advantages and limitations. We emphasize how these technologies have been applied to understand the dynamics of intestinal epithelial cells in homeostatic and injury-induced regeneration models.

scholarly journals Prevalent Presence of Periodic Actin-spectrin-based Membrane Skeleton in a Broad Range of Neuronal Cell Types and Animal Species

2016 ◽  
Author(s):  
Jiang He ◽  
Ruobo Zhou ◽  
Zhuhao Wu ◽  
Monica Carrasco ◽  
Peri Kurshan ◽  
...  
Keyword(s):  
Glial Cell ◽  
Animal Species ◽  
Homo Sapiens ◽  
Neuronal Cell ◽  
Cell Types ◽  
Membrane Skeleton ◽  
Brain Regions ◽  
Inhibitory Neurons ◽  
Periodic Distribution ◽  
Neuronal Types

AbstractActin, spectrin and associated molecules form a periodic, sub-membrane cytoskeleton in the axons of neurons. For a better understanding of this membrane-associated periodic skeleton (MPS), it is important to address how prevalent this structure is in different neuronal types, different subcellular compartments, and across different animal species. Here, we investigated the organization of spectrin in a variety of neuronal and glial-cell types. We observed the presence of MPS in all of the tested neuronal types cultured from mouse central and peripheral nervous systems, including excitatory and inhibitory neurons from several brain regions, as well as sensory and motor neurons. Quantitative analyses show that MPS is preferentially formed in axons in all neuronal types tested here: spectrin shows a long-range, periodic distribution throughout all axons, but only appears periodic in a small fraction of dendrites, typically in the form of isolated patches in sub-regions of these dendrites. As in dendrites, we also observed patches of periodic spectrin structures in a small fraction of glial-cell processes in four types of glial cells cultured from rodent tissues. Interestingly, despite its strong presence in the axonal shaft, MPS is absent in most presynaptic boutons, but is present in a substantial fraction of dendritic spine necks, including some projecting from dendrites where such a periodic structure is not observed in the shaft. Finally, we found that spectrin is capable of adopting a similar periodic organization in neurons of a variety of animal species, including Caenorhabditis elegans, Drosophila, Gallus gallus, Mus musculus and Homo sapiens.

scholarly journals SETD4-expressing cells contribute to pancreatic development and response to cerulein induced pancreatitis injury

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Jin-Ze Tian ◽  
Sheng Xing ◽  
Jing-Yi Feng ◽  
Shu-Hua Yang ◽  
Yan-Fu Ding ◽  
...  
Keyword(s):  
Cell Population ◽  
Acinar Cells ◽  
Pancreatic Disease ◽  
Lineage Tracing ◽  
Genetic Lineage ◽  
Pancreatic Development ◽  
Histone Lysine Methyltransferase ◽  
Population Potential ◽  
Potential Applications ◽  
Genetic Lineage Tracing

AbstractIn the adult pancreas, the presence of progenitor or stem cells and their potential involvement in homeostasis and regeneration remains unclear. Here, we identify that SET domain-containing protein 4 (SETD4), a histone lysine methyltransferase, is expressed in a small cell population in the adult mouse pancreas. Genetic lineage tracing shows that during pancreatic development, descendants of SETD4+ cells make up over 70% of pancreatic cells and then contribute to each pancreatic lineage during pancreatic homeostasis. SETD4+ cells generate newborn acinar cells in response to cerulein-induced pancreatitis in acinar compartments. Ablation of SETD4+ cells compromises regeneration of acinar cells, in contrast to controls. Our findings provide a new cellular narrative for pancreatic development, homeostasis and response to injury via a small SETD4+ cell population. Potential applications may act to preserve pancreatic function in case of pancreatic disease and/or damage.

scholarly journals Hlf Expression Marks Early Emergence of Hematopoietic Stem Cell Precursors With Adult Repopulating Potential and Fate

2021 ◽  
Vol 9 ◽  
Author(s):  
Wanbo Tang ◽  
Jian He ◽  
Tao Huang ◽  
Zhijie Bai ◽  
Chaojie Wang ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mouse Model ◽  
Hematopoietic Stem Cells ◽  
Fetal Liver ◽  
Lineage Tracing ◽  
Genetic Lineage ◽  
Hematopoietic Stem ◽  
Genetic Lineage Tracing

In the aorta-gonad-mesonephros (AGM) region of mouse embryos, pre-hematopoietic stem cells (pre-HSCs) are generated from rare and specialized hemogenic endothelial cells (HECs) via endothelial-to-hematopoietic transition, followed by maturation into bona fide hematopoietic stem cells (HSCs). As HECs also generate a lot of hematopoietic progenitors not fated to HSCs, powerful tools that are pre-HSC/HSC-specific become urgently critical. Here, using the gene knockin strategy, we firstly developed an Hlf-tdTomato reporter mouse model and detected Hlf-tdTomato expression exclusively in the hematopoietic cells including part of the immunophenotypic CD45– and CD45+ pre-HSCs in the embryonic day (E) 10.5 AGM region. By in vitro co-culture together with long-term transplantation assay stringent for HSC precursor identification, we further revealed that unlike the CD45– counterpart in which both Hlf-tdTomato-positive and negative sub-populations harbored HSC competence, the CD45+ E10.5 pre-HSCs existed exclusively in Hlf-tdTomato-positive cells. The result indicates that the cells should gain the expression of Hlf prior to or together with CD45 to give rise to functional HSCs. Furthermore, we constructed a novel Hlf-CreER mouse model and performed time-restricted genetic lineage tracing by a single dose induction at E9.5. We observed the labeling in E11.5 AGM precursors and their contribution to the immunophenotypic HSCs in fetal liver (FL). Importantly, these Hlf-labeled early cells contributed to and retained the size of the HSC pool in the bone marrow (BM), which continuously differentiated to maintain a balanced and long-term multi-lineage hematopoiesis in the adult. Therefore, we provided another valuable mouse model to specifically trace the fate of emerging HSCs during development.

scholarly journals Unraveling the transcriptional networks that drive oligodendrocyte fate specification in Sonic hedgehog-responsive neocortical progenitors

2020 ◽  
Author(s):  
Caitlin C. Winkler ◽  
Luuli N. Tran ◽  
Ellyn P. Milan ◽  
Fernando García-Moreno ◽  
Santos J. Franco
Keyword(s):  
Sonic Hedgehog ◽  
Wild Type Mouse ◽  
Lineage Tracing ◽  
Human Embryos ◽  
Transcriptional Networks ◽  
Genetic Lineage ◽  
Gene Regulatory ◽  
Oligodendrocyte Precursor ◽  
Genetic Lineage Tracing ◽  
Developing Nervous System

In the developing nervous system, progenitors first generate neurons before making astrocytes and oligodendrocytes. We previously showed that increased Sonic hedgehog (Shh) signaling in dorsal forebrain progenitors is important for their production of oligodendrocytes as neurogenesis winds down. Here, we analyzed single-cell RNA sequencing datasets to better understand how Shh controls this neuron-to-oligodendrocyte switch in the neocortex. We first identified Shh-responding progenitors using a dataset in which Shh was overexpressed in the mouse dorsal forebrain. Pseudotime trajectory inferences revealed a subpopulation committed to the oligodendrocyte precursor cell (OPC) lineage. Genes upregulated along this lineage defined a pre-OPC state, as cells transitioned from progenitors to OPCs. Using several datasets from wild-type mouse and human embryos at different ages, we confirmed a pre-OPC state preceding OPC emergence during normal development. Finally, we show that pre-OPCs are enriched for a gene regulatory network involving the transcription factor Ascl1. Genetic lineage-tracing demonstrated Ascl1+ dorsal progenitors primarily make oligodendrocytes. We propose a model in which Shh shifts the balance between opposing transcriptional networks toward an Ascl1 lineage, thereby facilitating the switch between neurogenesis and oligodendrogenesis.

Symptoms, Related Brain Regions, and Diagnosis

2013 ◽  
Author(s):  
J. Eric Ahlskog
Keyword(s):  
Spinal Cord ◽  
Nervous System ◽  
Basal Ganglia ◽  
Brain Stem ◽  
Muscle Activation ◽  
Sensory Information ◽  
Brain Regions ◽  
Electrical Signal ◽  
Brain And Spinal Cord ◽  
The Brain

As a prelude to the treatment chapters that follow, we need to define and describe the types of problems and symptoms encountered in DLB and PDD. The clinical picture can be quite varied: problems encountered by one person may be quite different from those encountered by another person, and symptoms that are problematic in one individual may be minimal in another. In these disorders, the Lewy neurodegenerative process potentially affects certain nervous system regions but spares others. Affected areas include thinking and memory circuits, as well as movement (motor) function and the autonomic nervous system, which regulates primary functions such as bladder, bowel, and blood pressure control. Many other brain regions, by contrast, are spared or minimally involved, such as vision and sensation. The brain and spinal cord constitute the central nervous system. The interface between the brain and spinal cord is by way of the brain stem, as shown in Figure 4.1. Thought, memory, and reasoning are primarily organized in the thick layers of cortex overlying lower brain levels. Volitional movements, such as writing, throwing, or kicking, also emanate from the cortex and integrate with circuits just below, including those in the basal ganglia, shown in Figure 4.2. The basal ganglia includes the striatum, globus pallidus, subthalamic nucleus, and substantia nigra, as illustrated in Figure 4.2. Movement information is integrated and modulated in these basal ganglia nuclei and then transmitted down the brain stem to the spinal cord. At spinal cord levels the correct sequence of muscle activation that has been programmed is accomplished. Activated nerves from appropriate regions of the spinal cord relay the signals to the proper muscles. Sensory information from the periphery (limbs) travels in the opposite direction. How are these signals transmitted? Brain cells called neurons have long, wire-like extensions that interface with other neurons, effectively making up circuits that are slightly similar to computer circuits; this is illustrated in Figure 4.3. At the end of these wire-like extensions are tiny enlargements (terminals) that contain specific biological chemicals called neurotransmitters. Neurotransmitters are released when the electrical signal travels down that neuron to the end of that wire-like process.

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