Gli3 is required for Emx gene expression during dorsal telencephalon development

Development ◽  
1999 ◽  
Vol 126 (16) ◽  
pp. 3561-3571 ◽  
Author(s):  
T. Theil ◽  
G. Alvarez-Bolado ◽  
A. Walter ◽  
U. Ruther
Keyword(s):  
Gene Expression ◽  
Dentate Gyrus ◽  
Molecular Level ◽  
Null Mutation ◽  
Mouse Mutant ◽  
Dorsal Midline ◽  
Forebrain Development ◽  
Emotional Behaviour ◽  
Molecular Information ◽  
Dorsal Telencephalon

Dentate gyrus and hippocampus as centers for spatial learning, memory and emotional behaviour have been the focus of much interest in recent years. The molecular information on its development, however, has been relatively poor. To date, only Emx genes were known to be required for dorsal telencephalon development. Here, we report on forebrain development in the extra toes (Xt(J)) mouse mutant which carries a null mutation of the Gli3 gene. This defect leads to a failure to establish the dorsal di-telencephalic junction and finally results in a severe size reduction of the neocortex. In addition, Xt(J)/Xt(J) mice show absence of the hippocampus (Ammon's horn plus dentate gyrus) and the choroid plexus in the lateral ventricle. The medial wall of the telencephalon, which gives rise to these structures, fails to invaginate during embryonic development. On a molecular level, disruption of dorsal telencephalon development in Xt(J)/Xt(J) embryos correlates with a loss of Emx1 and Emx2 expression. Furthermore, the expression of Fgf8 and Bmp4 in the dorsal midline of the telencephalon is altered. However, expression of Shh, which is negatively regulated by Gli3 in the spinal cord, is not affected in the Xt(J)/Xt(J) forebrain. This study therefore implicates Gli3 as a key regulator for the development of the dorsal telencephalon and implies Gli3 to be upstream of Emx genes in a genetic cascade controlling dorsal telencephalic development.

Signaling in new directions

1995 ◽  
Vol 73 (3-4) ◽  
pp. 133-136 ◽  
Author(s):  
Haleh Vahidi Samiei
Keyword(s):  
Gene Expression ◽  
Signal Transduction ◽  
Tyrosine Kinase ◽  
Map Kinase ◽  
Receptor Tyrosine Kinase ◽  
Tyrosine Kinases ◽  
Receptor Tyrosine Kinases ◽  
Molecular Level ◽  
Clear Cut ◽  
New Directions

Many laboratories, using a variety of organisms, have contributed to deciphering the identity and the order of the components leading from ligand-bound receptor tyrosine kinases to various intracellular events, including changes in gene expression. The gaps have only been filled recently. This minireview summarizes the findings and points out the degree of conservation of the same pathway in distant organisms, both at the molecular level and in terms of the consecutive steps. The review also looks at points at which this pathway might be diverging and points onto which other pathways might be converging. These interactions are not always clear cut, and understanding them will be the challenge for the future.Key words: signal transduction, receptor tyrosine kinase, RAS, RAF, MAP kinase.

scholarly journals Stochastic Kinetic Analysis of Developmental Pathway Bifurcation in Phage λ-Infected Escherichia coli Cells

Genetics ◽  
1998 ◽  
Vol 149 (4) ◽  
pp. 1633-1648 ◽  
Author(s):  
Adam Arkin ◽  
John Ross ◽  
Harley H McAdams
Keyword(s):  
Gene Expression ◽  
Kinetic Model ◽  
Kinetic Analysis ◽  
Molecular Level ◽  
Host Responses ◽  
Statistical Thermodynamic ◽  
Regulatory Systems ◽  
Regulatory Circuit ◽  
Phenotype Selection ◽  
Decision Circuit

Abstract Fluctuations in rates of gene expression can produce highly erratic time patterns of protein production in individual cells and wide diversity in instantaneous protein concentrations across cell populations. When two independently produced regulatory proteins acting at low cellular concentrations competitively control a switch point in a pathway, stochastic variations in their concentrations can produce probabilistic pathway selection, so that an initially homogeneous cell population partitions into distinct phenotypic subpopulations. Many pathogenic organisms, for example, use this mechanism to randomly switch surface features to evade host responses. This coupling between molecular-level fluctuations and macroscopic phenotype selection is analyzed using the phage λ lysis-lysogeny decision circuit as a model system. The fraction of infected cells selecting the lysogenic pathway at different phage:cell ratios, predicted using a molecular-level stochastic kinetic model of the genetic regulatory circuit, is consistent with experimental observations. The kinetic model of the decision circuit uses the stochastic formulation of chemical kinetics, stochastic mechanisms of gene expression, and a statistical-thermodynamic model of promoter regulation. Conventional deterministic kinetics cannot be used to predict statistics of regulatory systems that produce probabilistic outcomes. Rather, a stochastic kinetic analysis must be used to predict statistics of regulatory outcomes for such stochastically regulated systems.

Emx1 and Emx2 functions in development of dorsal telencephalon

Development ◽  
1997 ◽  
Vol 124 (1) ◽  
pp. 101-111 ◽  
Author(s):  
M. Yoshida ◽  
Y. Suda ◽  
I. Matsuo ◽  
N. Miyamoto ◽  
N. Takeda ◽  
...  
Keyword(s):  
Dentate Gyrus ◽  
Expression Patterns ◽  
Lateral Shift ◽  
Cerebral Hemispheres ◽  
Limbic Cortex ◽  
Lateral Region ◽  
Gap Gene ◽  
Positive Region ◽  
Dorsal Telencephalon ◽  
And Behavior

The genes Emx1 and Emx2 are mouse cognates of a Drosophila head gap gene, empty spiracles, and their expression patterns have suggested their involvement in regional patterning of the forebrain. To define their functions we introduced mutations into these loci. The newborn Emx2 mutants displayed defects in archipallium structures that are believed to play essential roles in learning, memory and behavior: the dentate gyrus was missing, and the hippocampus and medial limbic cortex were greatly reduced in size. In contrast, defects were subtle in adult Emx1 mutant brain. In the early developing Emx2 mutant forebrain, the evagination of cerebral hemispheres was reduced and the roof between the hemispheres was expanded, suggesting the lateral shift of its boundary. Defects were not apparent, however, in the region where Emx1 expression overlaps that of Emx2, nor was any defect found in the early embryonic forebrain caused by mutation of the Emx1 gene, of which expression principally occurs within the Emx2-positive region. Emx2 most likely delineates the palliochoroidal boundary in the absence of Emx1 expression during early dorsal forebrain patterning. In the more lateral region of telencephalon, Emx2-deficiency may be compensated for by Emx1 and vice versa. Phenotypes of newborn brains also suggest that these genes function in neurogenesis corresponding to their later expressions.

scholarly journals Exposure to Paper Mill Effluent at a Site in North Central Florida Elicits Molecular-Level Changes in Gene Expression Indicative of Progesterone and Androgen Exposure

PLoS ONE ◽  
2014 ◽  
Vol 9 (9) ◽  
pp. e106644 ◽  
Author(s):  
Erica K. Brockmeier ◽  
B. Sumith Jayasinghe ◽  
William E. Pine ◽  
Krystan A. Wilkinson ◽  
Nancy D. Denslow
Keyword(s):  
Gene Expression ◽  
Molecular Level ◽  
Paper Mill ◽  
North Central ◽  
Paper Mill Effluent ◽  
Central Florida ◽  
Androgen Exposure ◽  
A Site

Analyzing Gene Expression through Real Time PCR while Neo-tissue Regeneration using Developed Tissue Constructs

2020 ◽  
pp. 15-34
Keyword(s):  
Gene Expression ◽  
Real Time ◽  
Tissue Regeneration ◽  
Real Time Pcr ◽  
Molecular Level ◽  
Northern Blotting ◽  
Tissue Constructs ◽  
Low Sensitivity

Real-time PCR offers a wide area of application to analyze the role of gene activity in various biological aspects at the molecular level with higher specificity, sensitivity and the potential to troubleshoot with post-PCR processing and difficulties. With the recent advancement in the development of functional tissue graft for the regeneration of damaged/diseased tissue, it is effective to analyze the cell behaviour and differentiation over tissue construct toward specific lineage through analyzing the expression of an array of specific genes. With the ability to collect data in the exponential phase, the application of Real-Time PCR has been expanded into various fields such as tissue engineering ranging from absolute quantification of gene expression to determine neo-tissue regeneration and its maturation. In addition to its usage as a research tool, numerous advancements in molecular diagnostics have been achieved, including microbial quantification, determination of gene dose and cancer research. Also, in order to consistently quantify mRNA levels, Northern blotting and in situ hybridization (ISH) methods are less preferred due to low sensitivity, poor precision in detecting gene expression at a low level. An amplification step is thus frequently required to quantify mRNA amounts from engineered tissues of limited size. When analyzing tissue-engineered constructs or studying biomaterials–cells interactions, it is pertinent to quantify the performance of such constructs in terms of extracellular matrix formation while in vitro and in vivo examination, provide clues regarding the performance of various tissue constructs at the molecular level. In this chapter, our focus is on Basics of qPCR, an overview of technical aspects of Real-time PCR; recent Protocol used in the lab, primer designing, detection methods and troubleshooting of the experimental problems.

The Neuromolecular Brain

Neuro ◽  
2013 ◽  
Author(s):  
Nikolas Rose ◽  
Joelle M. Abi-Rached
Keyword(s):  
Gene Expression ◽  
Synaptic Plasticity ◽  
Learning And Memory ◽  
Time Scales ◽  
Molecular Level ◽  
Human Life ◽  
Neuronal Circuits ◽  
Molecular Processes ◽  
Nerve Development ◽  
The Brain

This chapter examines the neuromolecular and plastic brain. Ideas about plasticity and the openness of brains to environment influences, from initial evidence about nerve development, through the recognition that synaptic plasticity was the very basis of learning and memory, to evidence about the influence of environment on gene expression and the persistence throughout life of the capacity to make new neurons—all this made the neuromolecular brain seem exquisitely open to its milieu, with changes at the molecular level occurring throughout the course of a human life and thus shaping the growth, organization, and regeneration of neurons and neuronal circuits at time scales from the millisecond to the decade. This was an opportunity to explore the myriad ways in which the milieu got “under the skin,” implying an openness of these molecular processes of the brain to biography, sociality, and culture, and hence perhaps even to history and politics.

scholarly journals An Algorithm for the Stochastic Simulation of Gene Expression and Heterogeneous Population Dynamics

2011 ◽  
Vol 9 (1) ◽  
pp. 89-112 ◽  
Author(s):  
Daniel A. Charlebois ◽  
Jukka Intosalmi ◽  
Dawn Fraser ◽  
Mads Kærn
Keyword(s):  
Gene Expression ◽  
Population Dynamics ◽  
Steady State ◽  
Stochastic Simulation ◽  
Molecular Level ◽  
Single Cells ◽  
Heterogeneous Population ◽  
Population Heterogeneity ◽  
Time Dependent ◽  
Cell Populations

AbstractWe present an algorithm for the stochastic simulation of gene expression and heterogeneous population dynamics. The algorithm combines an exact method to simulate molecular-level fluctuations in single cells and a constant-number Monte Carlo method to simulate time-dependent statistical characteristics of growing cell populations. To benchmark performance, we compare simulation results with steady-state and time-dependent analytical solutions for several scenarios, including steady-state and time-dependent gene expression, and the effects on population heterogeneity of cell growth, division, and DNA replication. This comparison demonstrates that the algorithm provides an efficient and accurate approach to simulate how complex biological features influence gene expression. We also use the algorithm to model gene expression dynamics within “bet-hedging” cell populations during their adaption to environmental stress. These simulations indicate that the algorithm provides a framework suitable for simulating and analyzing realistic models of heterogeneous population dynamics combining molecular-level stochastic reaction kinetics, relevant physiological details and phenotypic variability.

scholarly journals A null mutation in the Bacillus subtilis aconitase gene causes a block in Spo0A-phosphate-dependent gene expression.

1997 ◽  
Vol 179 (23) ◽  
pp. 7351-7359 ◽  
Author(s):  
J E Craig ◽  
M J Ford ◽  
D C Blaydon ◽  
A L Sonenshein
Keyword(s):  
Gene Expression ◽  
Bacillus Subtilis ◽  
Null Mutation

scholarly journals Stress-induced gene expression and behavior are controlled by DNA methylation and methyl donor availability in the dentate gyrus

2016 ◽  
Vol 113 (17) ◽  
pp. 4830-4835 ◽  
Author(s):  
Emily A. Saunderson ◽  
Helen Spiers ◽  
Karen R. Mifsud ◽  
Maria Gutierrez-Mecinas ◽  
Alexandra F. Trollope ◽  
...  
Keyword(s):  
Gene Expression ◽  
Dna Methylation ◽  
Dentate Gyrus ◽  
Crucial Role ◽  
Histone H3 ◽  
Behavioral Responses ◽  
Cpg Methylation ◽  
Granule Neurons ◽  
Methyl Donor ◽  
And Behavior

Stressful events evoke long-term changes in behavioral responses; however, the underlying mechanisms in the brain are not well understood. Previous work has shown that epigenetic changes and immediate-early gene (IEG) induction in stress-activated dentate gyrus (DG) granule neurons play a crucial role in these behavioral responses. Here, we show that an acute stressful challenge [i.e., forced swimming (FS)] results in DNA demethylation at specific CpG (5′-cytosine–phosphate–guanine-3′) sites close to the c-Fos (FBJ murine osteosarcoma viral oncogene homolog) transcriptional start site and within the gene promoter region of Egr-1 (early growth response protein 1) specifically in the DG. Administration of the (endogenous) methyl donor S-adenosyl methionine (SAM) did not affect CpG methylation and IEG gene expression at baseline. However, administration of SAM before the FS challenge resulted in an enhanced CpG methylation at the IEG loci and suppression of IEG induction specifically in the DG and an impaired behavioral immobility response 24 h later. The stressor also specifically increased the expression of the de novo DNA methyltransferase Dnmt3a [DNA (cytosine-5-)-methyltransferase 3 alpha] in this hippocampus region. Moreover, stress resulted in an increased association of Dnmt3a enzyme with the affected CpG loci within the IEG genes. No effects of SAM were observed on stress-evoked histone modifications, including H3S10p-K14ac (histone H3, phosphorylated serine 10 and acetylated lysine-14), H3K4me3 (histone H3, trimethylated lysine-4), H3K9me3 (histone H3, trimethylated lysine-9), and H3K27me3 (histone H3, trimethylated lysine-27). We conclude that the DNA methylation status of IEGs plays a crucial role in FS-induced IEG induction in DG granule neurons and associated behavioral responses. In addition, the concentration of available methyl donor, possibly in conjunction with Dnmt3a, is critical for the responsiveness of dentate neurons to environmental stimuli in terms of gene expression and behavior.

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