Cerebellar histogenesis is disturbed in mice lacking cyclin D2

Development ◽  
1999 ◽  
Vol 126 (9) ◽  
pp. 1927-1935 ◽  
Author(s):  
J.M. Huard ◽  
C.C. Forster ◽  
M.L. Carter ◽  
P. Sicinski ◽  
M.E. Ross
Keyword(s):  
Granule Cell ◽  
Molecular Layer ◽  
Stellate Cells ◽  
Cell Types ◽  
Cell Number ◽  
Specific Cell ◽  
Cyclin D2 ◽  
Specific Expression ◽  
Precursor Pool ◽  
Cell Type Specific Expression

Formation of brain requires deftly balancing primary genesis of neurons and glia, detection of when sufficient cells of each type have been produced, shutdown of proliferation and removal of excess cells. The region and cell type-specific expression of cell cycle regulatory proteins, such as demonstrated for cyclin D2, may contribute to these processes. If so, regional brain development should be affected by alteration of cyclin expression. To test this hypothesis, the representation of specific cell types was examined in the cerebellum of animals lacking cyclin D2. The loss of this cyclin primarily affected two neuronal populations: granule cell number was reduced and stellate interneurons were nearly absent. Differences between null and wild-type siblings were obvious by the second postnatal week. Decreases in granule cell number arose from both reduction in primary neurogenesis and increase in apoptosis of cells that fail to differentiate. The dearth of stellate cells in the molecular layer indicates that emergence of this subpopulation requires cyclin D2 expression. Surprisingly, Golgi and basket interneurons, thought to originate from the same precursor pool as stellate cells, appear unaffected. These results suggest that cyclin D2 is required in cerebellum not only for proliferation of the granule cell precursors but also for proper differentiation of granule and stellate interneurons.

scholarly journals Adeno-Associated Virus Technologies and Methods for Targeted Neuronal Manipulation

2019 ◽  
Author(s):  
Leila Haery ◽  
Benjamin E. Deverman ◽  
Katherine Matho ◽  
Ali Cetin ◽  
Kenton Woodard ◽  
...  
Keyword(s):  
Viral Vectors ◽  
Cell Types ◽  
Regulatory Elements ◽  
Specific Cell ◽  
Specific Expression ◽  
Adeno Associated Virus ◽  
Cell Type Specific Expression ◽  
Cell Type Specific ◽  
And Function ◽  
Novel Applications

AbstractCell-type-specific expression of molecular tools and sensors is critical to construct circuit diagrams and to investigate the activity and function of neurons within the nervous system. Strategies for targeted manipulation include combinations of classical genetic tools such as Cre/loxP and Flp/FRT, use of cis-regulatory elements, targeted knock-in transgenic mice, and gene delivery by AAV and other viral vectors. The combination of these complex technologies with the goal of precise neuronal targeting is a challenge in the lab. This report will discuss the theoretical and practical aspects of combining current technologies and establish best practices for achieving targeted manipulation of specific cell types. Novel applications and tools, as well as areas for development, will be envisioned and discussed.

scholarly journals Cell-specific expression and individual function of prohormone convertase PC1/3 in Tribolium larval growth highlights major evolutionary changes between beetle and fly neuroendocrine systems

EvoDevo ◽  
2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Sonja Fritzsche ◽  
Vera S. Hunnekuhl
Keyword(s):  
Larval Growth ◽  
Neuroendocrine System ◽  
Small Subset ◽  
Specific Cell ◽  
Specific Expression ◽  
Individual Function ◽  
Evolutionary Changes ◽  
Cell Groups ◽  
Cell Type Specific Expression ◽  
And Function

Abstract Background The insect neuroendocrine system acts in the regulation of physiology, development and growth. Molecular evolution of this system hence has the potential to allow for major biological differences between insect groups. Two prohormone convertases, PC1/3 and PC2, are found in animals and both function in the processing of neuropeptide precursors in the vertebrate neurosecretory pathway. Whereas PC2-function is conserved between the fly Drosophila and vertebrates, ancestral PC1/3 was lost in the fly lineage and has not been functionally studied in any protostome. Results In order to understand its original functions and the changes accompanying the gene loss in the fly, we investigated PC1/3 and PC2 expression and function in the beetle Tribolium castaneum. We found that PC2 is broadly expressed in the nervous system, whereas surprisingly, PC1/3 expression is restricted to specific cell groups in the posterior brain and suboesophageal ganglion. Both proteases have parallel but non-redundant functions in adult beetles’ viability and fertility. Female infertility following RNAi is caused by a failure to deposit sufficient yolk to the developing oocytes. Larval RNAi against PC2 produced moulting defects where the larvae were not able to shed their old cuticle. This ecdysis phenotype was also observed in a small subset of PC1/3 knockdown larvae and was strongest in a double knockdown. Unexpectedly, most PC1/3-RNAi larvae showed strongly reduced growth, but went through larval moults despite minimal to zero weight gain. Conclusions The cell type-specific expression of PC1/3 and its essential requirement for larval growth highlight the important role of this gene within the insect neuroendocrine system. Genomic conservation in most insect groups suggests that it has a comparable individual function in other insects as well, which has been replaced by alternative mechanisms in flies.

scholarly journals Cell-type Specific Expression Quantitative Trait Loci Associated with Alzheimer Disease in Blood and Brain Tissue

2020 ◽  
Author(s):  
Devanshi Patel ◽  
Xiaoling Zhang ◽  
John J. Farrell ◽  
Jaeyoon Chung ◽  
Thor D. Stein ◽  
...  
Keyword(s):  
Gene Expression ◽  
Quantitative Trait ◽  
Expression Patterns ◽  
Regulation Of Gene Expression ◽  
Cell Types ◽  
Eqtl Analysis ◽  
Cell Type ◽  
Specific Expression ◽  
Cell Type Specific Expression ◽  
Cell Type Specific

ABSTRACTBecause regulation of gene expression is heritable and context-dependent, we investigated AD-related gene expression patterns in cell-types in blood and brain. Cis-expression quantitative trait locus (eQTL) mapping was performed genome-wide in blood from 5,257 Framingham Heart Study (FHS) participants and in brain donated by 475 Religious Orders Study/Memory & Aging Project (ROSMAP) participants. The association of gene expression with genotypes for all cis SNPs within 1Mb of genes was evaluated using linear regression models for unrelated subjects and linear mixed models for related subjects. Cell type-specific eQTL (ct-eQTL) models included an interaction term for expression of “proxy” genes that discriminate particular cell type. Ct-eQTL analysis identified 11,649 and 2,533 additional significant gene-SNP eQTL pairs in brain and blood, respectively, that were not detected in generic eQTL analysis. Of note, 386 unique target eGenes of significant eQTLs shared between blood and brain were enriched in apoptosis and Wnt signaling pathways. Five of these shared genes are established AD loci. The potential importance and relevance to AD of significant results in myeloid cell-types is supported by the observation that a large portion of GWS ct-eQTLs map within 1Mb of established AD loci and 58% (23/40) of the most significant eGenes in these eQTLs have previously been implicated in AD. This study identified cell-type specific expression patterns for established and potentially novel AD genes, found additional evidence for the role of myeloid cells in AD risk, and discovered potential novel blood and brain AD biomarkers that highlight the importance of cell-type specific analysis.

Viral Strategies for Targeting the Central and Peripheral Nervous Systems

2018 ◽  
Vol 41 (1) ◽  
pp. 323-348 ◽  
Author(s):  
Claire N. Bedbrook ◽  
Benjamin E. Deverman ◽  
Viviana Gradinaru
Keyword(s):  
Nervous System ◽  
Regulatory Elements ◽  
Specific Cell ◽  
Cell Type ◽  
Specific Expression ◽  
Recombinant Viruses ◽  
Neuronal Populations ◽  
Neuroscience Research ◽  
Cell Type Specific Expression ◽  
Cell Type Specific

Recombinant viruses allow for targeted transgene expression in specific cell populations throughout the nervous system. The adeno-associated virus (AAV) is among the most commonly used viruses for neuroscience research. Recombinant AAVs (rAAVs) are highly versatile and can package most cargo composed of desired genes within the capsid's ∼5-kb carrying capacity. Numerous regulatory elements and intersectional strategies have been validated in rAAVs to enable cell type–specific expression. rAAVs can be delivered to specific neuronal populations or globally throughout the animal. The AAV capsids have natural cell type or tissue tropism and trafficking that can be modified for increased specificity. Here, we describe recently engineered AAV capsids and associated cargo that have extended the utility of AAVs in targeting molecularly defined neurons throughout the nervous system, which will further facilitate neuronal circuit interrogation and discovery.

scholarly journals Cell type–specific expression of SEPT3-homology subgroup members controls the subunit number of heteromeric septin complexes

2014 ◽  
Vol 25 (10) ◽  
pp. 1594-1607 ◽  
Author(s):  
Mikael E. Sellin ◽  
Sonja Stenmark ◽  
Martin Gullberg
Keyword(s):  
Animal Cell ◽  
Building Blocks ◽  
Cell Types ◽  
Specific Expression ◽  
Tissue Specific ◽  
Cell Type Specific Expression ◽  
A Subunit ◽  
Cell Type Specific ◽  
Genetically Manipulated ◽  
Differential Properties

Septins are filament-forming proteins important for organizing the cortex of animal and fungal cells. In mammals, 13 septin paralogues were recently shown to assemble into core heterohexamer and heterooctamer complexes, which serve as building blocks for apolar filamentous structures that differ among cell types. To determine how tissue-specific septin paralogue expression may shape core heteromer repertoires and thereby modulate properties of septin filaments, we devised protocols to analyze native septin heteromers with distinct numbers of subunits. Our evidence based on genetically manipulated human cells supports and extends recent concepts of homology subgroup–restricted assembly into distinct categories of apolar heterohexamers and heterooctamers. We also identify a category of tetramers that have a subunit composition equivalent to an octameric building block. These atypical tetramers are prevalent in lymphocytes and neural tissues, in which octamers are abundant but hexamers are rare. Our results can be explained by tissue-specific expression of SEPT3 subgroup members: SEPT3, SEPT9, and SEPT12. These serve as cognate subunits in either heterooctamers or atypical tetramers but exhibit different preferences in various tissues. The identified tissue-specific repertoires of septin heteromers provide insights into how higher-order septin structures with differential properties and stabilities may form in diverse animal cell types.

scholarly journals Dynamics of gene expression in single root cells ofA. thaliana

2018 ◽  
Author(s):  
Ken Jean-Baptiste ◽  
José L. McFaline-Figueroa ◽  
Cristina M. Alexandre ◽  
Michael W. Dorrity ◽  
Lauren Saunders ◽  
...  
Keyword(s):  
Gene Expression ◽  
Single Cell ◽  
Developmental Trajectories ◽  
Cell Types ◽  
Cell Type ◽  
Specific Expression ◽  
Root Cells ◽  
Cell Lineages ◽  
Cell Type Specific Expression ◽  
Cell Type Specific

ABSTRACTSingle-cell RNA-seq can yield high-resolution cell-type-specific expression signatures that reveal new cell types and the developmental trajectories of cell lineages. Here, we apply this approach toA. thalianaroot cells to capture gene expression in 3,121 root cells. We analyze these data with Monocle 3, which orders single cell transcriptomes in an unsupervised manner and uses machine learning to reconstruct single-cell developmental trajectories along pseudotime. We identify hundreds of genes with cell-type-specific expression, with pseudotime analysis of several cell lineages revealing both known and novel genes that are expressed along a developmental trajectory. We identify transcription factor motifs that are enriched in early and late cells, together with the corresponding candidate transcription factors that likely drive the observed expression patterns. We assess and interpret changes in total RNA expression along developmental trajectories and show that trajectory branch points mark developmental decisions. Finally, by applying heat stress to whole seedlings, we address the longstanding question of possible heterogeneity among cell types in the response to an abiotic stress. Although the response of canonical heat shock genes dominates expression across cell types, subtle but significant differences in other genes can be detected among cell types. Taken together, our results demonstrate that single-cell transcriptomics holds promise for studying plant development and plant physiology with unprecedented resolution.

scholarly journals Differential induction of Pax genes by NGF and BDNF in cerebellar primary cultures.

1994 ◽  
Vol 125 (2) ◽  
pp. 417-425 ◽  
Author(s):  
C Kioussi ◽  
P Gruss
Keyword(s):  
Gene Family ◽  
Expression Patterns ◽  
Primary Cultures ◽  
Neuronal Cell ◽  
Cell Types ◽  
Early Gene ◽  
Specific Expression ◽  
Pax Genes ◽  
Cell Type Specific Expression

The Pax genes encode sequence-specific DNA binding transcription factors that are expressed in embryonic development of the nervous system. Primary neuronal cell cultures derived from the cerebellar cortex of embryonic day 14, newborn and 7-d old mice, were used to investigate the cell-type specific expression patterns of three members of the murine paired box containing gene family (Pax gene family), in vitro. Cell types which express Pax-2, Pax-3, and Pax-6 RNA in primary cultures correspond to those found in regions of the cerebellum which show RNA signals in sections of the developing mouse brain. To find mechanisms regulating Pax gene expression during cerebellar development, the differential regulation of Pax-2, Pax-3, and Pax-6 by NGF and BDNF, two structurally related neurotrophins, was studied in such primary cultures. Pax-2 and Pax-6 RNA increased slightly by 1 h and remained elevated throughout a 24-h treatment with BDNF and NGF. Pax-3 RNA was not detected in newborn cultures, but underwent a rapid (1 h) and transient (2 h) induction upon treatment with either BDNF or NGF. No response was seen with EGF or FGF. Cycloheximide treatment amplified Pax-3 induction and prolonged the signal. Thus, Pax-3 induction resembles that of the immediate-early gene c-fos, which transduces growth factor signals during the development of particular neuronal/glial cell types. The changes in Pax expression were inductive rather than trophic.

scholarly journals Cell-Type Specific Analysis of Selenium-Related Genes in Brain

Antioxidants ◽  
2019 ◽  
Vol 8 (5) ◽  
pp. 120
Author(s):  
Alexandru R. Sasuclark ◽  
Vedbar S. Khadka ◽  
Matthew W. Pitts
Keyword(s):  
Neural Development ◽  
Cortical Neurons ◽  
Cell Types ◽  
Inhibitory Neurons ◽  
Brain Atlas ◽  
Cell Type ◽  
Specific Expression ◽  
Rnaseq Data ◽  
Cell Type Specific Expression ◽  
Cell Type Specific

Selenoproteins are a unique class of proteins that play key roles in redox signaling in the brain. This unique organ is comprised of a wide variety of cell types that includes excitatory neurons, inhibitory neurons, astrocytes, microglia, and oligodendrocytes. Whereas selenoproteins are known to be required for neural development and function, the cell-type specific expression of selenoproteins and selenium-related machinery has yet to be systematically investigated. Due to advances in sequencing technology and investment from the National Institutes of Health (NIH)-sponsored BRAIN initiative, RNA sequencing (RNAseq) data from thousands of cortical neurons can now be freely accessed and searched using the online RNAseq data navigator at the Allen Brain Atlas. Hence, we utilized this newly developed tool to perform a comprehensive analysis of the cell-type specific expression of selenium-related genes in brain. Select proteins of interest were further verified by means of multi-label immunofluorescent labeling of mouse brain sections. Of potential significance to neural selenium homeostasis, we report co-expression of selenoprotein P (SELENOP) and selenium binding protein 1 (SELENBP1) within astrocytes. These findings raise the intriguing possibility that SELENBP1 may negatively regulate astrocytic SELENOP synthesis and thereby limit downstream Se supply to neurons.

scholarly journals Functional annotation of lncRNA in high-throughput screening

2021 ◽  
Author(s):  
Chi Wai Yip ◽  
Divya M. Sivaraman ◽  
Anika V. Prabhu ◽  
Jay W. Shin
Keyword(s):  
High Throughput ◽  
High Throughput Screening ◽  
Functional Annotation ◽  
Cell Types ◽  
Specific Expression ◽  
Functional Roles ◽  
Cellular Processes ◽  
Cell Type Specific Expression ◽  
Cell Type Specific ◽  
Different Cell Types

Abstract Recent efforts on the characterization of long non-coding RNAs (lncRNAs) revealed their functional roles in modulating diverse cellular processes. These include pluripotency maintenance, lineage commitment, carcinogenesis, and pathogenesis of various diseases. By interacting with DNA, RNA and protein, lncRNAs mediate multifaceted mechanisms to regulate transcription, RNA processing, RNA interference and translation. Of more than 173000 discovered lncRNAs, the majority remain functionally unknown. The cell type-specific expression and localization of the lncRNA also suggest potential distinct functions of lncRNAs across different cell types. This highlights the niche of identifying functional lncRNAs in different biological processes and diseases through high-throughput (HTP) screening. This review summarizes the current work performed and perspectives on HTP screening of functional lncRNAs where different technologies, platforms, cellular responses and the downstream analyses are discussed. We hope to provide a better picture in applying different technologies to facilitate functional annotation of lncRNA efficiently.

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