Spatiotemporal gene expression is the activation

Gene expression

Gene expression is the process by which information from a gene is used in the synthesis of a functional gene product. These products are often proteins, but in non-protein coding genes such as ribosomal RNA , transfer RNA or small nuclear RNA genes, the product is a functional RNA...

 of gene

Gene

A gene is a molecular unit of heredity of a living organism. It is a name given to some stretches of DNA and RNA that code for a type of protein or for an RNA chain that has a function in the organism. Living beings depend on genes, as they specify all proteins and functional RNA chains...

s within specific tissues

Biological tissue

Tissue is a cellular organizational level intermediate between cells and a complete organism. A tissue is an ensemble of cells, not necessarily identical, but from the same origin, that together carry out a specific function. These are called tissues because of their identical functioning...

 of an organism at specific times during development

Developmental biology

Developmental biology is the study of the process by which organisms grow and develop. Modern developmental biology studies the genetic control of cell growth, differentiation and "morphogenesis", which is the process that gives rise to tissues, organs and anatomy.- Related fields of study...

. 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

Cell type

A cell type is a distinct morphological or functional form of cell. When a cell switches state from one cell type to another, it undergoes cellular differentiation. A list of distinct cell types in the adult human body may include several hundred distinct types.-References:...

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

WNT

WNT is a three-letter abbreviation with multiple meanings, as described below:*Windows NT*WNT *Wnt signaling pathway, a complex protein network...

 family of genes. In the early embryonic development of the model organism Drosophila melanogaster

Drosophila melanogaster

Drosophila melanogaster is a species of Diptera, or the order of flies, in the family Drosophilidae. The species is known generally as the common fruit fly or vinegar fly. Starting from Charles W...

, 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

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 form, for instance, the wings or legs or antennae or other...

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

Symmetry breaking

Symmetry breaking in physics describes a phenomenon where small fluctuations acting on a system which is crossing a critical point decide the system's fate, by determining which branch of a bifurcation is taken. To an outside observer unaware of the fluctuations , the choice will appear arbitrary...

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

Oocyte

An oocyte, ovocyte, or rarely ocyte, 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 the ovary during female gametogenesis. The female germ cells produce a primordial germ cell which undergoes a mitotic...

 because maternal cells deposit messenger RNA

Messenger RNA

Messenger RNA is a molecule of RNA encoding a chemical "blueprint" for a protein product. mRNA is transcribed from a DNA template, and carries coding information to the sites of protein synthesis: the ribosomes. Here, the nucleic acid polymer is translated into a polymer of amino acids: a protein...

 (mRNA) for these genes in the poles of the egg before it is laid

Oviposition

Oviposition is the process of laying eggs by oviparous animals.Some arthropods, for example, lay their eggs with an organ called the ovipositor.Fish , amphibians, reptiles, birds and monetremata also lay eggs....

.

Identifying spatiotemporal patterns

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

Reporter gene

In molecular biology, a reporter gene is a gene that researchers attach to a regulatory sequence of another gene of interest in cell culture, animals or plants. Certain genes are chosen as reporters because the characteristics they confer on organisms expressing them are easily identified and...

 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

Green fluorescent protein

The green fluorescent protein is a protein composed of 238 amino acid residues that exhibits bright green fluorescence when exposed to blue light. Although many other marine organisms have similar green fluorescent proteins, GFP traditionally refers to the protein first isolated from the...

 can be visualized by stimulating it with blue light and then using a digital camera

Digital camera

A digital camera is a camera that takes video or still photographs, or both, digitally by recording images via an electronic image sensor. It is the main device used in the field of digital photography...

 to record green fluorescent

Fluorescence

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

 emission.

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

Immunohistochemistry

Immunohistochemistry or IHC refers to the process of detecting antigens in cells of a tissue section by exploiting the principle of antibodies binding specifically to antigens in biological tissues. IHC takes its name from the roots "immuno," in reference to antibodies used in the procedure, and...

 involves preparing an antibody

Antibody

An antibody, also known as an immunoglobulin, is a large Y-shaped protein used by the immune system to identify and neutralize foreign objects such as bacteria and viruses. The antibody recognizes a unique part of the foreign target, termed an antigen...

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

Half-life, abbreviated t½, is the period of time it takes for the amount of a substance undergoing decay to decrease by half. The name was originally used to describe a characteristic of unstable atoms , but it may apply to any quantity which follows a set-rate decay.The original term, dating to...

 relative to the mRNA that is used to translate

Translation (genetics)

In molecular biology and genetics, translation is the third stage of protein biosynthesis . In translation, messenger RNA produced by transcription is decoded by the ribosome to produce a specific amino acid chain, or polypeptide, that will later fold into an active protein...

 the protein, this can lead to distorted interpretation of which cells are expressing the mRNA.
In situ hybridization

In situ hybridization

In situ hybridization is a type of hybridization that uses a labeled complementary DNA or RNA strand to localize a specific DNA or RNA sequence in a portion or section of tissue , or, if the tissue is small enough , in the entire tissue...

 is an alternate method in which a "probe," a synthetic nucleic acid

Nucleic acid

Nucleic acids are biological molecules essential for life, and include DNA and RNA . Together with proteins, nucleic acids make up the most important macromolecules; each is found in abundance in all living things, where they function in encoding, transmitting and expressing genetic information...

 with a sequence complementary

Complementarity (molecular biology)

In molecular biology, complementarity is a property of double-stranded nucleic acids such as DNA, as well as DNA:RNA duplexes. Each strand is complementary to the other in that the base pairs between them are non-covalently connected via two or three hydrogen bonds...

 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

DNA sequence

The sequence or primary structure of a nucleic acid is the composition of atoms that make up the nucleic acid and the chemical bonds that bond those atoms. Because nucleic acids, such as DNA and RNA, are unbranched polymers, this specification is equivalent to specifying the sequence of...

 of DNA

DNA

Deoxyribonucleic acid is a nucleic acid that contains the genetic instructions used in the development and functioning of all known living organisms . The DNA segments that carry this genetic information are called genes, but other DNA sequences have structural purposes, or are involved in...

 corresponding to the gene of interest.

A method called enhancer-trap

Enhancer trap

An enhancer trap is a transgenic construction for the identification of enhancers, produced by the fusing of two proteins, genes for which are inserted into the genome. The enhancer trap structure contains a mobile element usually some sort of P element and a reporter gene...

 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

Fixation (histology)

In the fields of histology, pathology, and cell biology, fixation is a chemical process by which biological tissues are preserved from decay, thereby preventing autolysis or putrefaction...

 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.

External links

• FlyBase report of wingless expression in fruit flies
• Browse spatiotemporal gene expression patterns organized by human chromosome number
• https://www.genevestigator.comSpatiotemporal gene expression in Genevestigator
  Genevestigator
  Genevestigator is a web-based application developed for biologists and medical researchers to rapidly find out in which tissues, at which stages of development, and to what stimuli, drug treatments, diseases, or genetic modifications genes of given organisms are activated...
  
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• Search for mammalian genes with particular expression patterns
• Expression patterns during Drosophila embryogenesis as inferred by in situ hybridization