scholarly journals GENETIC AND DEVELOPMENTAL ANALYSIS OF THE LOCUS vnd IN DROSOPHILA MELANOGASTER

Genetics ◽  
1983 ◽  
Vol 104 (3) ◽  
pp. 433-448
Author(s):  
Kalpana White ◽  
Normand L DeCelles ◽  
Thomas C Enlow
Keyword(s):  
Neural Development ◽  
Gene Function ◽  
Imaginal Disc ◽  
Thoracic Ganglion ◽  
Neural Cells ◽  
Genetic Mosaics ◽  
Hypomorphic Mutation ◽  
Embryonic Lethal ◽  
Developmental Analysis ◽  
New Alleles

ABSTRACT Genetic and developmental analysis of an X-linked vital locus vnd was undertaken. Embryos hemizygous for the original allele vnd did not hatch and exhibited a disorganized ventral nervous system (VNS). The mutation maps in the region 1B6-7 to 1B9-10, a subregion of an area previously shown to be essential to normal neural development. In this paper, we report isolation of five new alleles at the locus vnd. Genetic complementation analysis of all mutations at the vnd locus, with lethal alleles at adjacent loci, indicates that all lesions at the locus vnd affect only one vital gene function in the region. Four of the five alleles are embryonic lethal; one allele is subvital and behaves like an hypomorphic mutation. Hemizygous embryos for three of the four embryonic lethal alleles were inspected in histological sections; all exhibited disorganized VNS similar to the original allele. The developmental analysis in gynandromorphic genetic mosaics shows that (1) vnd  + gene function is not essential in most imaginal-disc cell derivatives, (2) only about 30% of the mosaic zygotes survive as adults, (3) mosaic zygotes with mutant tissue close to the head cuticle are least likely to survive, and (4) mutant tissue in the thoracic ganglion in the adult is not necessarily lethal. The mosaic data are consistent with the vnd  + gene function being necessary in neural cells derived from the anterioventral region of the blastoderm.

scholarly journals Zika Virus Infection Leads to Demyelination and Axonal Injury in Mature CNS Cultures

Viruses ◽  
2021 ◽  
Vol 13 (1) ◽  
pp. 91
Author(s):  
Verena Schultz ◽  
Stephanie L. Cumberworth ◽  
Quan Gu ◽  
Natasha Johnson ◽  
Claire L. Donald ◽  
...  
Keyword(s):  
Nervous System ◽  
Neural Development ◽  
Zika Virus ◽  
Developmental Stages ◽  
Cell Types ◽  
Neural Cells ◽  
Zikv Infection ◽  
Axonal Pathology ◽  
Time Frames

Understanding how Zika virus (Flaviviridae; ZIKV) affects neural cells is paramount in comprehending pathologies associated with infection. Whilst the effects of ZIKV in neural development are well documented, impact on the adult nervous system remains obscure. Here, we investigated the effects of ZIKV infection in established mature myelinated central nervous system (CNS) cultures. Infection incurred damage to myelinated fibers, with ZIKV-positive cells appearing when myelin damage was first detected as well as axonal pathology, suggesting the latter was a consequence of oligodendroglia infection. Transcriptome analysis revealed host factors that were upregulated during ZIKV infection. One such factor, CCL5, was validated in vitro as inhibiting myelination. Transferred UV-inactivated media from infected cultures did not damage myelin and axons, suggesting that viral replication is necessary to induce the observed effects. These data show that ZIKV infection affects CNS cells even after myelination—which is critical for saltatory conduction and neuronal function—has taken place. Understanding the targets of this virus across developmental stages including the mature CNS, and the subsequent effects of infection of cell types, is necessary to understand effective time frames for therapeutic intervention.

Control of dorsoventral pattern in vertebrate neural development: induction and polarizing properties of the floor plate

Development ◽  
1991 ◽  
Vol 113 (Supplement_2) ◽  
pp. 105-122 ◽  
Author(s):  
Marysia Placzek ◽  
Toshiya Yamada ◽  
Marc Tessier-Lavigne ◽  
Thomas Jessell ◽  
Jane Dodd
Keyword(s):  
Neural Tube ◽  
Neural Development ◽  
Cell Types ◽  
Floor Plate ◽  
Neural Cells ◽  
Dorsoventral Patterning ◽  
Cellular Mechanisms ◽  
Cell Position

Distinct classes of neural cells differentiate at specific locations within the embryonic vertebrate nervous system. To define the cellular mechanisms that control the identity and pattern of neural cells we have used a combination of functional assays and antigenic markers to examine the differentiation of cells in the developing spinal cord and hindbrain in vivo and in vitro. Our results suggest that a critical step in the dorsoventral patterning of the embryonic CNS is the differentiation of a specialized group of midline neural cells, termed the floor plate, in response to local inductive signals from the underlying notochord. The floor plate and notochord appear to control the pattern of cell types that appear along the dorsoventral axis of the neural tube. The fate of neuroepithelial cells in the ventral neural tube may be defined by cell position with respect to the ventral midline and controlled by polarizing signals that originate from the floor plate and notochord.

scholarly journals Neural stemness contributes to cell tumorigenicity

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Liyang Xu ◽  
Min Zhang ◽  
Lihua Shi ◽  
Xiaoli Yang ◽  
Lu Chen ◽  
...  
Keyword(s):  
Cancer Cells ◽  
Progenitor Cells ◽  
Neural Development ◽  
Ground State ◽  
Cell Types ◽  
Bioinformatic Analysis ◽  
Neural Cells ◽  
Differentiation Potential ◽  
Neural Genes ◽  
Neural Stem Progenitor Cells

Abstract Background Previous studies demonstrated the dependence of cancer on nerve. Recently, a growing number of studies reveal that cancer cells share the property and regulatory network with neural stem/progenitor cells. However, relationship between the property of neural stemness and cell tumorigenicity is unknown. Results We show that neural stem/progenitor cells, but not non-neural embryonic or somatic stem/progenitor cell types, exhibit tumorigenicity and the potential for differentiation into tissue types of all germ layers when they are placed in non-native environment by transplantation into immunodeficient nude mice. Likewise, cancer cells capable of tumor initiation have the property of neural stemness because of their abilities in neurosphere formation in neural stem cell-specific serum-free medium and in differentiation potential, in addition to their neuronal differentiation potential that was characterized previously. Moreover, loss of a pro-differentiation factor in myoblasts, which have no tumorigenicity, lead to the loss of myoblast identity, and gain of the property of neural stemness, tumorigenicity and potential for re-differentiation. By contrast, loss of neural stemness via differentiation results in the loss of tumorigenicity. These suggest that the property of neural stemness contributes to cell tumorigenicity, and tumor phenotypic heterogeneity might be an effect of differentiation potential of neural stemness. Bioinformatic analysis reveals that neural genes in general are correlated with embryonic development and cancer, in addition to their role in neural development; whereas non-neural genes are not. Most of neural specific genes emerged in typical species representing transition from unicellularity to multicellularity during evolution. Genes in Monosiga brevicollis, a unicellular species that is a closest known relative of metazoans, are biased toward neural cells. Conclusions We suggest that the property of neural stemness is the source of cell tumorigenicity. This is due to that neural biased unicellular state is the ground state for multicellularity and hence cell type diversification or differentiation during evolution, and tumorigenesis is a process of restoration of neural ground state in somatic cells along a default route that is pre-determined by an evolutionary advantage of neural state.

scholarly journals Neural stemness contributes to cell tumorigenicity

2020 ◽  
Author(s):  
Liyang Xu ◽  
Min Zhang ◽  
Lihua Shi ◽  
Xiaoli Yang ◽  
Lu Chen ◽  
...  
Keyword(s):  
Cancer Cells ◽  
Progenitor Cells ◽  
Neural Development ◽  
Ground State ◽  
Cell Types ◽  
Bioinformatic Analysis ◽  
Neural Cells ◽  
Differentiation Potential ◽  
Neural Genes ◽  
Neural Stem Progenitor Cells

Abstract Background: Previous studies demonstrated the dependence of cancer on nerve. Recently, a growing number of studies reveal that cancer cells share the property and regulatory network with neural stem/progenitor cells. However, relationship between the property of neural stemness and cell tumorigenicity is unknown.Results: We show that neural stem/progenitor cells, but not non-neural embryonic or somatic stem/progenitor cell types, exhibit tumorigenicity and the potential for differentiation into tissue types of all germ layers when they are placed in non-native environment by transplantation into immunodeficient nude mice. Likewise, cancer cells capable of tumor initiation have the property of neural stemness because of their abilities in neurosphere formation in neural stem cell-specific serum-free medium and in differentiation potential, in addition to their neuronal differentiation potential that was characterized previously. Moreover, loss of a pro-differentiation factor in myoblasts, which have no tumorigenicity, lead to the loss of myoblast identity, and gain of the property of neural stemness, tumorigenicity and potential for re-differentiation. By contrast, loss of neural stemness via differentiation results in the loss of tumorigenicity. These suggest that the property of neural stemness contributes to cell tumorigenicity, and tumor phenotypic heterogeneity might be an effect of differentiation potential of neural stemness. Bioinformatic analysis reveals that neural genes in general are correlated with embryonic development and cancer, in addition to their role in neural development; whereas non-neural genes are not. Most of neural specific genes emerged in typical species representing transition from unicellularity to multicellularity during evolution. Genes in Monosiga brevicollis, a unicellular species that is a closest known relative of metazoans, are biased toward neural cells.Conclusions: We suggest that the property of neural stemness is the source of cell tumorigenicity. This is due to that neural biased unicellular state is the ground state for multicellularity and hence cell type diversification or differentiation during evolution, and tumorigenesis is a process of restoration of neural ground state in somatic cells along a default route that is pre-determined by an evolutionary advantage of neural state.

scholarly journals Three ENU-induced alleles of the murine quaking locus are recessive embryonic lethal mutations

1988 ◽  
Vol 51 (2) ◽  
pp. 95-102 ◽  
Author(s):  
Monica J. Justice ◽  
Vernon C. Bode
Keyword(s):  
Mouse Chromosome ◽  
Lethal Mutation ◽  
Chromosome 17 ◽  
Wild Type ◽  
Embryonic Survival ◽  
Lethal Mutations ◽  
Embryonic Lethal ◽  
Embryonic Lethal Mutations ◽  
Precise Time ◽  
New Alleles

SummaryThe quaking (qk) locus on mouse chromosome 17 has been defined by a single viable quaking allele. Three new alleles of quaking were selected after ENU mutagenesis by their failure to complement the quaking phenotype. The qkk2 allele was induced on wild-type chromatin and the qkkt1 and qkkt4 alleles were induced on t-chromatin. Each is a recessive embryonic lethal mutation. They fail to complement each other and are not complemented by the deletion, TtOrl. Homozygotes and hemizygotes die at 8–9·5 days gestation, but not at a single precise time. Because the classical quaking mutation complements the lethality of these new alleles, but they fail to complement its quaking phenotype (myelination defect), we conclude that the quaking+ function is required for embryonic survival as well as for myelination.

A novel strategy for identifying mutations that sensitize Drosophila eye development to caffeine and hydroxyurea

Genome ◽  
2006 ◽  
Vol 49 (11) ◽  
pp. 1416-1427 ◽  
Author(s):  
E.A. Silva ◽  
B.J. Lee ◽  
L.S. Caceres ◽  
D. Renouf ◽  
B.R. Vilay ◽  
...  
Keyword(s):  
Gene Function ◽  
Imaginal Disc ◽  
Essential Gene ◽  
Cellular Responses ◽  
Multiple Alleles ◽  
Gene Mutant ◽  
Nonessential Gene ◽  
Disc Cells ◽  
Complementation Groups ◽  
Novel Strategy

This report describes a novel strategy for isolating Drosophila mutants with conditional eye phenotypes that should be generally applicable for identifying genes required for cellular responses to specific drugs. To test the strategy, we screened 3 of the 5 major chromosome arms for hydroxyurea- and (or) caffeine-sensitive (huc) mutants, and isolated mutations affecting 5 different complementation groups. Most of these were represented by single alleles; however, we also isolated multiple alleles of huc29DE gene, an essential gene that is also associated with a nonconditional pupal lethal phenotype. We also identified huc95E mutants, which are extremely sensitive to caffeine. Although huc95E is a nonessential gene, mutant imaginal disc cells undergo caffeine-dependent apoptosis, and huc95E gene function is required for the viability of the organism when mutant larvae are exposed to levels of caffeine that controls can easily tolerate. We have mapped the cytological positions of huc29D and huc95E as a first step toward molecularly characterizing the relevant genes.

scholarly journals Neural stemness contributes to cell tumorigenicity

2020 ◽  
Author(s):  
Liyang Xu ◽  
Min Zhang ◽  
Lihua Shi ◽  
Xiaoli Yang ◽  
Lu Chen ◽  
...  
Keyword(s):  
Cancer Cells ◽  
Progenitor Cells ◽  
Neural Development ◽  
Ground State ◽  
Cell Types ◽  
Bioinformatic Analysis ◽  
Neural Cells ◽  
Differentiation Potential ◽  
Neural Genes ◽  
Neural Stem Progenitor Cells

Abstract Background Previous studies demonstrated the dependence of cancer on nerve. Recently, a growing number of studies reveal that cancer cells share the property and regulatory network with neural stem/progenitor cells. However, relationship between the property of neural stemness and cell tumorigenicity is unknown. Results We show that neural stem/progenitor cells, but not non-neural embryonic or somatic stem/progenitor cell types, exhibit tumorigenicity and the potential for differentiation into tissue types of all germ layers when they are placed in non-native environment by transplantation into immunodeficient nude mice. Likewise, cancer cells capable of tumor initiation have the property of neural stemness because of their abilities in neurosphere formation in neural stem cell-specific serum-free medium and in differentiation potential, in addition to their neuronal differentiation potential that was characterized previously. Moreover, loss of a pro-differentiation factor in myoblasts, which have no tumorigenicity, lead to the loss of myoblast identity, and gain of the property of neural stemness, tumorigenicity and potential for re-differentiation. These suggest that the property of neural stemness contributes to cell tumorigenicity, and tumor phenotypic heterogeneity might be an effect of differentiation potential of neural stemness. Bioinformatic analysis reveals that neural genes in general are correlated with embryonic development and cancer, in addition to their role in neural development; whereas non-neural genes are not. Most of neural specific genes emerged in typical species representing transition from unicellularity to multicellularity during evolution. Genes in Monosiga brevicollis, a unicellular species that is a closest known relative of metazoans, are biased toward neural cells. Conclusions We suggest that the property of neural stemness is the source of cell tumorigenicity. This is due to that neural biased unicellular state is the ground state for multicellularity and hence cell type diversification or differentiation during evolution, and tumorigenesis is a process of restoration of neural ground state in somatic cells along a default route that is pre-determined by an evolutionary advantage of neural state.

scholarly journals CHD8 regulates the balance between proliferation and differentiation of human iPSCs in neural development

2019 ◽  
Author(s):  
Wenzhong Liu ◽  
Weilai Dong ◽  
Ellen J. Hoffman ◽  
Thomas V. Fernandez ◽  
Abha R. Gupta
Keyword(s):  
Cell Cycle ◽  
Cell Proliferation ◽  
Neural Development ◽  
Neural Differentiation ◽  
Neural Progenitor Cells ◽  
Autism Spectrum ◽  
Neural Cells ◽  
Neuronal Marker ◽  
Human Ipscs ◽  
M Phase

ABSTRACTBackgroundChromodomain helicase DNA-binding protein 8 (CHD8), which encodes a chromatin remodeling protein that regulates Wnt/β-catenin mediated gene expression, is one of the most strongly associated genes with autism spectrum disorder (ASD). Characterization of ASD patients with CHD8 disrupting mutations and animal and stem cell models of CHD8 deficiency suggest that CHD8 plays a role in neurodevelopment.MethodsWe generated iPSCs from the T-lymphocytes of a healthy, typically-developing human male and iPSC lines from the same source which were subjected to CRISPR/Cas9-mediated knockdown (KD) of CHD8. We subsequently derived neural progenitor cells (NPCs) and neural cells and examined the effects of CHD8 deficiency on cell proliferation and neural differentiation.ResultsWe observed that, compared to WT, CHD8 KD: (1) increased the number of iPSC colonies formed, (2) suppressed spontaneous differentiation along the edges of iPSC colonies, (3) increased the proliferation of NPCs, (4) delayed the formation of neural rosettes, (5) delayed neurite outgrowth, (6) decreased the percentage of cells in the G0/G1 phase of the cell cycle, (7) increased the percentage of cells in the G2/M phase of the cell cycle, (8) decreased presence of the neuronal marker MAP2 although not the glial marker GFAP, (9) decreased presence for the excitatory neuronal marker VGLUT1, and (10) decreased presence of the synaptic marker SYN1.ConclusionsOur results suggest that CHD8 deficiency causes alterations in the cell cycle. More specifically, CHD8 KD appears to increase cell proliferation and delay neural differentiation. This may contribute to the pathophysiology of ASD.

scholarly journals Glycosylphosphatidylinositol Biosynthesis and Remodeling are Required for Neural Crest Cell, Cardiac and Neural Development

2019 ◽  
Author(s):  
Marshall Lukacs ◽  
Tia Roberts ◽  
Praneet Chatuverdi ◽  
Rolf W. Stottmann
Keyword(s):  
Neural Crest ◽  
Neural Development ◽  
Cleft Lip ◽  
Cleft Lip And Palate ◽  
Folate Receptor ◽  
Neural Crest Cell ◽  
Specific Expression ◽  
Hypomorphic Mutation ◽  
Pathogenic Variants ◽  
Cleft Lip Palate

AbstractThe glycosylphosphatidylinositol (GPI) anchor attaches nearly 150 proteins to the cell surface. Patients with pathogenic variants in GPI biosynthetic pathway genes display an array of phenotypes including seizures, developmental delay, dysmorphic facial features and cleft palate. There is virtually no mechanism to explain these phenotypes. we identified a novel mouse mutant (cleft lip/palate, edema and exencephaly; Clpex) with a hypomorphic mutation in Post-Glycophosphatidylinositol Attachment to Proteins-2 (Pgap2). Pgap2 is one of the final proteins in the GPI biosynthesis pathway and is required for anchor maturation. We found the Clpex mutation results in a global decrease in surface GPI expression. Surprisingly, Pgap2 showed tissue specific expression with enrichment in the affected tissues of the Clpex mutant. We found the phenotype in Clpex mutants is due to apoptosis of neural crest cells (NCCs) and the cranial neuroepithelium, as is observed in the GPI anchored Folate Receptor 1-/- mouse. We showed folinic acid supplementation in utero can rescue the cleft lip phenotype in Clpex. Finally, we generated a novel mouse model of NCC-specific total GPI deficiency in the Wnt1-Cre lineage. These mutants developed median cleft lip and palate demonstrating a cell autonomous role for GPI biosynthesis in NCC development.

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