Spatiotemporal gene expression is the

activation Activation, in chemistry and biology, is the process whereby something is prepared or excited for a subsequent reaction. Chemistry In chemistry, "activation" refers to the reversible transition of a molecule into a nearly identical chemical o ...

gene In biology, the word gene (from , ; "... Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity..." meaning ''generation'' or ''birth'' or ''gender'') can have several different meanings. The Mendelian gene is a b ...

s within specific tissues of an organism at specific times during

development Development or developing may refer to: Arts *Development hell, when a project is stuck in development *Filmmaking, development phase, including finance and budgeting *Development (music), the process thematic material is reshaped * Photograph ...

. Gene activation patterns vary widely in complexity. Some are straightforward and static, such as the pattern of ''tubulin,'' which is expressed in all cells at all times in life. Some, on the other hand, are extraordinarily intricate and difficult to predict and model, with expression fluctuating wildly from minute to minute or from cell to cell. Spatiotemporal variation plays a key role in generating the diversity of

cell type A cell type is a classification used to identify cells that share morphological or phenotypical features. A multicellular organism may contain cells of a number of widely differing and specialized cell types, such as muscle cells and skin cell ...

s found in developed organisms; since the identity of a cell is specified by the collection of genes actively expressed within that cell, if gene expression was uniform spatially and temporally, there could be at most one kind of cell. Consider the gene ''wingless,'' a member of the wnt family of genes. In the early embryonic development of the model organism ''

Drosophila melanogaster ''Drosophila melanogaster'' is a species of fly (the taxonomic order Diptera) in the family Drosophilidae. The species is often referred to as the fruit fly or lesser fruit fly, or less commonly the " vinegar fly" or "pomace fly". Starting with ...

'', or fruit fly, ''wingless'' is expressed across almost the entire embryo in alternating stripes three cells separated. This pattern is lost by the time the organism develops into a larva, but ''wingless'' is still expressed in a variety of tissues such as the wing

imaginal disc An imaginal disc is one of the parts of a holometabolous insect larva that will become a portion of the outside of the adult insect during the pupal transformation. Contained within the body of the larva, there are pairs of discs that will for ...

s, patches of tissue that will develop into the adult wings. The spatiotemporal pattern of ''wingless'' gene expression is determined by a

network Network, networking and networked may refer to: Science and technology * Network theory, the study of graphs as a representation of relations between discrete objects * Network science, an academic field that studies complex networks Mathematics ...

of regulatory interactions consisting of the effects of many different genes such as ''even-skipped'' and ''Krüppel.'' What causes spatial and temporal differences in the expression of a single gene? Because current expression patterns depend strictly on previous expression patterns, there is a regressive problem of explaining what caused the first differences in gene expression. The process by which uniform gene expression becomes spatially and temporally differential is known as

symmetry breaking In physics, symmetry breaking is a phenomenon in which (infinitesimally) small fluctuations acting on a system crossing a critical point decide the system's fate, by determining which branch of a bifurcation is taken. To an outside observe ...

. For example, in the case of embryonic ''Drosophila'' development, the genes ''nanos'' and ''bicoid'' are asymmetrically expressed in the

oocyte An oocyte (, ), oöcyte, or ovocyte is a female gametocyte or germ cell involved in reproduction. In other words, it is an immature ovum, or egg cell. An oocyte is produced in a female fetus in the ovary during female gametogenesis. The femal ...

because maternal cells deposit messenger RNA (mRNA) for these genes in the poles of the egg before it is laid.

Identifying spatiotemporal patterns

One way to identify the expression pattern of a particular gene is to place a

reporter gene In molecular biology, a reporter gene (often simply reporter) is a gene that researchers attach to a regulatory sequence of another gene of interest in bacteria, cell culture, animals or plants. Such genes are called reporters because the charac ...

downstream of its promoter. In this configuration, the promoter gene will cause the reporter gene to be expressed only where and when the gene of interest is expressed. The expression distribution of the reporter gene can be determined by visualizing it. For example, the reporter gene green fluorescent protein can be visualized by stimulating it with blue light and then using a

digital camera A digital camera is a camera that captures photographs in digital memory. Most cameras produced today are digital, largely replacing those that capture images on photographic film. Digital cameras are now widely incorporated into mobile devices ...

to record green

fluorescent Fluorescence is the emission of light by a substance that has absorbed light or other electromagnetic radiation. It is a form of luminescence. In most cases, the emitted light has a longer wavelength, and therefore a lower photon energy, ...

emission. If the promoter of the gene of interest is unknown, there are several ways to identify its spatiotemporal distribution. Immunohistochemistry involves preparing an

antibody An antibody (Ab), also known as an immunoglobulin (Ig), is a large, Y-shaped protein used by the immune system to identify and neutralize foreign objects such as pathogenic bacteria and viruses. The antibody recognizes a unique molecule of the ...

with specific affinity for the protein associated with the gene of interest. This distribution of this antibody can then be visualized by a technique such as fluorescent labeling. Immunohistochemistry has the advantages of being methodologically feasible and relatively inexpensive. Its disadvantages include non-specificity of the antibody leading to

false positive A false positive is an error in binary classification in which a test result incorrectly indicates the presence of a condition (such as a disease when the disease is not present), while a false negative is the opposite error, where the test resul ...

identification of expression. Poor penetrance of the antibody into the target tissue can lead to

false negative A false positive is an error in binary classification in which a test result incorrectly indicates the presence of a condition (such as a disease when the disease is not present), while a false negative is the opposite error, where the test resul ...

results. Furthermore, since immunohistochemistry visualizes the protein generated by the gene, if the protein product diffuses between cells, or has a particularly short or long

half-life Half-life (symbol ) is the time required for a quantity (of substance) to reduce to half of its initial value. The term is commonly used in nuclear physics to describe how quickly unstable atoms undergo radioactive decay or how long stable at ...

relative to the

mRNA In molecular biology, messenger ribonucleic acid (mRNA) is a single-stranded molecule of RNA that corresponds to the genetic sequence of a gene, and is read by a ribosome in the process of synthesizing a protein. mRNA is created during the ...

that is used to

translate Translation is the communication of the meaning of a source-language text by means of an equivalent target-language text. The English language draws a terminological distinction (which does not exist in every language) between ''transl ...

the protein, this can lead to distorted interpretation of which cells are expressing the

. ''In situ'' hybridization is an alternate method in which a "probe," a synthetic nucleic acid with a sequence complementary to the mRNA of the gene, is added to the tissue. This probe is then chemically tagged so that it can be visualized later. This technique enables visualization specifically of mRNA-producing cells without any of the artifacts associated with immunohistochemistry. However, it is notoriously difficult, and requires knowledge of the

sequence In mathematics, a sequence is an enumerated collection of objects in which repetitions are allowed and order matters. Like a set, it contains members (also called ''elements'', or ''terms''). The number of elements (possibly infinite) is calle ...

of DNA corresponding to the gene of interest. A method called enhancer-trap screening reveals the diversity of spatiotemporal gene expression patterns possible in an organism. In this technique, DNA that encodes a reporter gene is randomly inserted into the genome. Depending on the gene promoters proximal to the insertion point, the reporter gene will be expressed in particular tissues at particular points in development. While enhancer-trap derived expression patterns do not necessarily reflect the actual patterns of expression of specific genes, they reveal the variety of spatiotemporal patterns that are accessible to evolution. Reporter genes can be visualized in living organisms, but both immunohistochemistry and ''in situ'' hybridization must be performed in

fixed Fixed may refer to: * ''Fixed'' (EP), EP by Nine Inch Nails * ''Fixed'', an upcoming 2D adult animated film directed by Genndy Tartakovsky * Fixed (typeface), a collection of monospace bitmap fonts that is distributed with the X Window System * ...

tissues. Techniques that require fixation of tissue can only generate a single temporal time point per individual organism. However, using live animals instead of fixed tissue can be crucial in dynamically understanding expression patterns over an individual's lifespan. Either way, variation between individuals can confound the interpretation of temporal expression patterns.

Methods to control spatiotemporal gene expression

Several methods are being pursued for controlling gene expression spatially, temporally and in different degrees. One method is by using

operon In genetics, an operon is a functioning unit of DNA containing a cluster of genes under the control of a single promoter. The genes are transcribed together into an mRNA strand and either translated together in the cytoplasm, or undergo splic ...

inducer/repressor system which provides temporal control of gene expression. To control gene expression spatially inkjet printers are under development for printing ligands on gel culture. Other popular method involves use of light to control gene expression in spatiotemporal fashion. Since light can also be controlled easily in space, time and degree, several methods of controlling gene expression at DNA and RNA level have been developed and are under study. For example, RNA interference can be controlled using light and also patterning of gene expression has been performed in cell monolayer and in zebrafish embryos using caged

morpholino A Morpholino, also known as a Morpholino oligomer and as a phosphorodiamidate Morpholino oligomer (PMO), is a type of oligomer molecule (colloquially, an oligo) used in molecular biology to modify gene expression. Its molecular structure contain ...

peptide nucleic acid Peptide nucleic acid (PNA) is an artificially synthesized polymer similar to DNA or RNA. Synthetic peptide nucleic acid oligomers have been used in recent years in molecular biology procedures, diagnostic assays, and antisense therapies. Due ...

demonstrating the control of gene expression spatiotemporally. Recently light based control has been shown at DNA level using transgene based system or caged triplex forming oligos

References

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External links

FlyBase report of ''wingless'' expression in fruit flies
* ttps://www.genevestigator.com Spatiotemporal gene expressionin

Genevestigator Genevestigator is an application consisting of a gene expression database and tools to analyse the data. It exists in two versions, biomedical and plant, depending on the species of the underlying microarray and RNAseq data. It was started in Janu ...

Search for mammalian genes with particular expression patternsExpression patterns during Drosophila embryogenesis as inferred by in situ hybridization
Molecular genetics Gene expression Space and time