scholarly journals Hectd1 regulates intracellular localization and secretion of Hsp90 to control cellular behavior of the cranial mesenchyme

2012 ◽  
Vol 196 (6) ◽  
pp. 789-800 ◽  
Author(s):  
Anjali A. Sarkar ◽  
Irene E. Zohn
Keyword(s):  
Neural Tube ◽  
Neural Tube Defect ◽  
Intracellular Localization ◽  
Cell Types ◽  
Abnormal Behavior ◽  
Data Set ◽  
Cellular Behavior ◽  
Multiple Cell ◽  
Mesenchyme Cells ◽  
And Behavior

Hectd1 mutant mouse embryos exhibit the neural tube defect exencephaly associated with abnormal cranial mesenchyme. Cellular rearrangements in cranial mesenchyme are essential during neurulation for elevation of the neural folds. Here we investigate the molecular basis of the abnormal behavior of Hectd1 mutant cranial mesenchyme. We demonstrate that Hectd1 is a functional ubiquitin ligase and that one of its substrates is Hsp90, a chaperone protein with both intra- and extracellular clients. Extracellular Hsp90 enhances migration of multiple cell types. In mutant cranial mesenchyme cells, both secretion of Hsp90 and emigration of cells from cranial mesenchyme explants were enhanced. Importantly, we show that this enhanced emigration was highly dependent on the excess Hsp90 secreted from mutant cells. Together, our data set forth a model whereby increased secretion of Hsp90 in the cranial mesenchyme of Hectd1 mutants is responsible, at least in part, for the altered organization and behavior of these cells and provides a potential molecular mechanism underlying the neural tube defect.

The winged-helix transcription factor Foxd3 suppresses interneuron differentiation and promotes neural crest cell fate

Development ◽  
2001 ◽  
Vol 128 (21) ◽  
pp. 4127-4138 ◽  
Author(s):  
Mirella Dottori ◽  
Michael K. Gross ◽  
Patricia Labosky ◽  
Martyn Goulding
Keyword(s):  
Transcription Factor ◽  
Neural Crest ◽  
Cell Fate ◽  
Neural Tube ◽  
Neural Crest Cell ◽  
Neural Crest Cells ◽  
Cell Types ◽  
Winged Helix ◽  
Multiple Cell ◽  
Winged Helix Transcription Factor

The neural crest is a migratory cell population that gives rise to multiple cell types in the vertebrate embryo. The intrinsic determinants that segregate neural crest cells from multipotential dorsal progenitors within the neural tube are poorly defined. In this study, we show that the winged helix transcription factor Foxd3 is expressed in both premigratory and migratory neural crest cells. Foxd3 is genetically downstream of Pax3 and is not expressed in regions of Pax3 mutant mice that lack neural crest, implying that Foxd3 may regulate aspects of the neural crest differentiation program. We show that misexpression of Foxd3 in the chick neural tube promotes a neural crest-like phenotype and suppresses interneuron differentiation. Cells that ectopically express Foxd3 upregulate HNK1 and Cad7, delaminate and emigrate from the neural tube at multiple dorsoventral levels. Foxd3 does not induce Slug and RhoB, nor is its ability to promote a neural crest-like phenotype enhanced by co-expression of Slug. Together these results suggest Foxd3 can function independently of Slug and RhoB to promote the development of neural crest cells from neural tube progenitors.

Moving Living Cells and Fluids on Microchips for Diagnostics

2008 ◽  
Author(s):  
Mehmet Toner
Keyword(s):  
Cancer Biology ◽  
Cell Types ◽  
Genetically Engineered ◽  
Cellular Systems ◽  
Screening Tools ◽  
Microfluidic Mixing ◽  
Cellular Behavior ◽  
Complex Interactions ◽  
Multiple Cell ◽  
Engineered Tissue

Biomedical applications of microfabricated devices is no longer limited to non-living systems as genes-on-a-chip or lab-on-a-chip, recent advances in the understanding of cellular behavior in microenvironments have started to pave the way toward living micro-devices. These emerging devices are expected to become key technologies in the 21st century of medicine with a broad range of applications varying from diagnostic, tissue engineered products, cell-based drug screening tools, and basic molecular biology tools. They will also include multiple cell types and/or genetically engineered cells to investigate complex interactions between cells from different tissues. These sophisticated devices will contain micro-engineered tissue units coupled to each other by complex microfluidic handling network. Microfluidic mixing systems will also precisely regulate the composition and concentration of drugs to be tested. This presentation will briefly review the early historical literature on the use of microtechnologies in cellular systems and then focus on various applications in cancer biology, HIV/AIDS and global health, inflammation, and systems biology. The presentation will primarily focus on interesting transport phenomena at the microscale and how such information can be used for the development of microfluidic systems for diagnostics and other applications.

scholarly journals Identifying sub-populations of cells in single cell transcriptomic data - a Bayesian mixture model approach to zero-inflation of counts

2021 ◽  
Author(s):  
Thomas Thorne
Keyword(s):  
Single Cell ◽  
Mixture Model ◽  
Dirichlet Process ◽  
Negative Binomial ◽  
Cell Types ◽  
Rna Seq ◽  
Dirichlet Process Mixture ◽  
Zero Inflation ◽  
Data Set ◽  
Multiple Cell

Single cell RNA-seq data exhibit large numbers of zero count values, that we demonstrate can, for a subset of transcripts, be better modelled by a zero inflated negative binomial distribution. We develop a novel Dirichlet process mixture model which employs both a mixture at the cell level to model multiple cell types, and a mixture of single cell RNA-seq counts at the transcript level to model the transcript specific zero-inflation of counts. It is shown that this approach outperforms previous approaches that applied multinomial distributions to model single cell RNA-seq counts, and also performer better or comparably to existing top performing methods. By taking a Bayesian approach we are able to build interpretable models of expression within clusters, and to quantify uncertainty in cluster assignments. Applied to a publicly available data set of single cell RNA-seq counts of multiple cell types from the mouse cortex and hippocampus, we demonstrate how our approach can be used to distinguish sub-populations of cells as clusters in the data, and to identify gene sets that are indicative of membership of a sub-population.

scholarly journals Independent Mutations in MouseVangl2That Cause Neural Tube Defects inLooptailMice Impair Interaction with Members of theDishevelledFamily

2004 ◽  
Vol 279 (50) ◽  
pp. 52703-52713 ◽  
Author(s):  
Elena Torban ◽  
Hui-Jun Wang ◽  
Normand Groulx ◽  
Philippe Gros
Keyword(s):  
Neural Tube ◽  
Neural Tube Defects ◽  
Neural Tube Defect ◽  
Planar Cell Polarity ◽  
Cell Types ◽  
Biochemical Properties ◽  
Model Organisms ◽  
Convergent Extension ◽  
Loss Of Function

Mammalian Vangl1 and Vangl2 are highly conserved membrane proteins that have evolved from a single ancestral proteinStrabismus/Van Goghfound inDrosophila. Mutations in theVangl2gene cause a neural tube defect (craniorachischisis) characteristic of thelooptail(Lp) mouse. Studies in model organisms indicate that Vangl proteins play a key developmental role in establishing planar cell polarity (PCP) and in regulating convergent extension (CE) movements during embryogenesis. The role of Vangl1 in these processes is virtually unknown, and the molecular function of Vangl1 and Vangl2 in PCP and CE is poorly understood. Using a yeast two-hybrid system, glutathioneS-transferase pull-down and co-immunoprecipitation assays, we show that both mouse Vangl1 and Vangl2 physically interact with the three members of the cytoplasmic Dishevelled (Dvl) protein family. This interaction is shown to require both the predicted cytoplasmic C-terminal half of Vangl1/2 and a portion of the Dvl protein containing PDZ and DIX domains. In addition, we show that the two knownVangl2loss-of-function mutations identified in two independentLpalleles associated with neural tube defects impair binding to Dvl1, Dvl2, and Dvl3. These findings suggest a molecular mechanism for the neural tube defect seen inLpmice. Our observations indicate that Vangl1 biochemical properties parallel those of Vangl2 and that Vangl1 might, therefore, participate in PCP and CE either in concert with Vangl2 or independently of Vangl2 in discrete cell types.

B12 Level May Predict Neural Tube Defect Risk

2009 ◽  
Vol 39 (6) ◽  
pp. 20
Author(s):  
ELIZABETH MECHCATIE
Keyword(s):  
Neural Tube ◽  
Neural Tube Defect

HCVS: Pinpointing Chromatin States Through Hierarchical Clustering and Visualization Scheme

2019 ◽  
Vol 14 (2) ◽  
pp. 148-156
Author(s):  
Nighat Noureen ◽  
Sahar Fazal ◽  
Muhammad Abdul Qadir ◽  
Muhammad Tanvir Afzal
Keyword(s):  
Hierarchical Clustering ◽  
Real Data ◽  
Cell Types ◽  
Computational Scheme ◽  
Data Set ◽  
Chromatin States ◽  
Functional Regions ◽  
Visualization Strategy ◽  
Hidden States ◽  
Next Generation Sequencing Ngs

Background: Specific combinations of Histone Modifications (HMs) contributing towards histone code hypothesis lead to various biological functions. HMs combinations have been utilized by various studies to divide the genome into different regions. These study regions have been classified as chromatin states. Mostly Hidden Markov Model (HMM) based techniques have been utilized for this purpose. In case of chromatin studies, data from Next Generation Sequencing (NGS) platforms is being used. Chromatin states based on histone modification combinatorics are annotated by mapping them to functional regions of the genome. The number of states being predicted so far by the HMM tools have been justified biologically till now. Objective: The present study aimed at providing a computational scheme to identify the underlying hidden states in the data under consideration. </P><P> Methods: We proposed a computational scheme HCVS based on hierarchical clustering and visualization strategy in order to achieve the objective of study. Results: We tested our proposed scheme on a real data set of nine cell types comprising of nine chromatin marks. The approach successfully identified the state numbers for various possibilities. The results have been compared with one of the existing models as well which showed quite good correlation. Conclusion: The HCVS model not only helps in deciding the optimal state numbers for a particular data but it also justifies the results biologically thereby correlating the computational and biological aspects.

An economic analysis of prenatal fetoscopic versus open neural tube defect repair

2020 ◽  
Author(s):  
B. C. King ◽  
J. Hagan ◽  
R. Corroenne ◽  
A. A. Shamshirsaz ◽  
J. Espinoza ◽  
...  
Keyword(s):  
Economic Analysis ◽  
Neural Tube ◽  
Neural Tube Defect ◽  
Defect Repair

scholarly journals Multiple cell types contribute to the atherosclerotic lesion fibrous cap by PDGFRβ and bioenergetic mechanisms

2021 ◽  
Vol 3 (2) ◽  
pp. 166-181 ◽  
Author(s):  
Alexandra A. C. Newman ◽  
Vlad Serbulea ◽  
Richard A. Baylis ◽  
Laura S. Shankman ◽  
Xenia Bradley ◽  
...  
Keyword(s):  
Atherosclerotic Lesion ◽  
Cell Types ◽  
Fibrous Cap ◽  
Multiple Cell
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