Gap gene

Segmentation genes determine the number and internal organization of the segments during embryogenesis of insects. Explore them were exhibited in the model organism Drosophila melanogaster, primarily through analysis of genes mutated flies or their embryos, the malformation of segmentation or the body outline. The genes have names that are usually derived from mutations that led to their discovery. Gene product of the segmentation genes are proteins with regulatory functions, which attach themselves to the DNA, and thus other genes almost like a switch on and off, these are called transcription factors. To the target genes have sequences, which are arranged on the DNA strand of the protein coding gene segment and themselves are not transcribed. Since the front end of a DNA strand will be referred to as " cis" end (the rear as the " trans" ), one speaks of " cis-regulatory " sections, or cis- elements. The transcription factors of the segmentation genes are connected in series in a regulatory cascade, which means that overall, early pronounced segmentation genes later on or off depending on its location in the developing embryo. It develops as a stripe pattern of successively arranged strips, in each of which a particular Segmentierungsgen (or a group of such ) is active. Through this cell strip the later segmentation of the body is represented. The cells that build up the body tissue itself obtained by the segmentation genes as information about their location in the developing organism. Depending on where they can grow, divide and differentiate or die (programmed cell death or apoptosis).

Subsequent analyzes have shown that homologous genes of many segmentation genes occur throughout the animal kingdom at all then studied organisms, they organize throughout the formation of the body axis. This is done in non-segmented organisms in a very similar and analogous manner. Other segmentation genes are only in insects or arthropods pronounced, some even only in the Diptera ( Diptera ), individual are even known exclusively from Drosophila.

The regulatory cascade

The embryo of the fruit fly Drosophila develops from the egg by an outer layer of cells, the blastoderm, a central yolk grows around. Within the blastoderm differentiates itself a germ band. In the first division steps only divide the nuclei, while the cytoplasm is not divided by cell membranes, such undivided association is called syncytium. Morphologically, no structure can be seen at this stage, the front and the rear end of the developing embryo look alike. Through experiments in the 1960s and 1970s it was shown that the longitudinal body axis, however, is already determined at this stage. It was found that the organizing factor, which determines the longitudinal body axis, is already given to the egg from the mother. This is based on substances which are concentrated in the front or rear Eipolen. Mutations in these genes lead to severe malformations, such as is created twice instead of the system on the front part, the back half. Since the respective gene products ( transcripts ) are derived from the mother, the corresponding genes, maternal genes are called. The into the cytoplasm of the egg transferred products of maternal genes thus define the front and rear end of the embryo. Your proteins form in the embryo from a concentration gradient ( a gradient ), in which some occur at the front end in the highest concentration, some at the back end. The intervening cells contain two of each different proportions, depending on how far forward the rear btw they are. Depending on the concentration of the proteins of maternal genes, a group of other genes in the embryo is then activated, the gap genes ( often taken from English, gap genes ) are called. The naming is based on that the mutation in one of these genes to the embryo body all portions missing. In Drosophila, five gap genes exist. Each gap genes now activated depending on the location, another gene of another class, the pair rule genes ( engl. pair rule gene). The name comes from here to the fact that a mutation in the embryo has only half the number of segments. Thus, the embryo is organized in seven stripes. The pair rule genes activate the segment polarization genes as the next class. Each strip is thereby divided into two strips. Thus, the fourteen body segments of the maggot are represented. ( In fact, the issue is more complicated: it can be preformed so-called para- segments, each consisting of the front end and the rear end of the adjacent segment ).

In the finished organism these segments, however, are not mutually morphologically similar, but differentiate into body sections ( tagmata ): head, torso (thorax) and abdomen ( tummy). Depending on the circumstances, different attachments and other organs such as antennae, legs, etc., are trained or not. This identity is allocated to divisions by another gene class, the Hox genes. In Drosophila, there are eight Hox genes. The expression of Hox genes is not linked closely to the segment sequence. Some segments of the body express the same Hox gene in the other two of which are expressed.

A total of approximately 40 to 50 genes have been identified that are involved in this pattern formation, the role of some of them is still unclear. A similar signal sequence, are also involved in the maternal and embryonic genes defines the dorsal - ventral axis of the embryo fixed, ie determined over the top ( back side ) and bottom ( ventral side ). These genes have been discovered later and a total of less well known.

Maternal genes

The maternal genes are, as the name suggests, in the maternal organism active. Their gene products, mostly RNA ( transcripts ), rare ready-made proteins are given to the developing egg. The genes Caudal ( cad ) and Hunchback ( hb ) have a dual role, they are both maternally as well as transcribed in the embryo itself later. The most important maternal genes that specify the orientation of the longitudinal body axis, is Bicoid ( bcd ). The Bicoid - protein defines the front end of the embryo is activated and, depending on the concentration of other genes in rearwardly advancing zones of different widths. Cad and Hb are initially almost uniformly distributed in the egg. However, since Bcd inhibits their expression, they accumulate in the back. The rear end of the egg, a further group of RNAs and proteins is enriched.

Gap genes

The name Lückengen ( engl. gap genes ) due to the fact that a loss of function of these genes in gaps in the segmentation, the lack of body segments leads. They are responsible for the division into a front, middle and rear. Among the eleven currently known gap genes include the Giant (gt or gat ), Hunchback ( hb), Knirps ( kni ), cripple ( in engl. Mostly " cripple " ) ( kr) and Tailless ( tll ). gad and hb have a dual role. They are both maternally (of maternal origin ) and in the embryo itself expressed. The gap genes are expressed initially distributed relatively widely and limited by self-assembly later on the matching strips. As well as the products of the maternal genes, the expressed transcription factors, only a short time is active. Their activity ends when the pattern has been formed and the following steps are initiated, which is already the case after about two hours of development time. Later in the organism, they no longer play a role, in part, however, they are independent of their role in the determination of the body axis in further pattern formation processes involved.

The expression of the gap genes is regulated by a combination of maternal genes and interactions between the gap genes themselves. In addition, plays a role at the cell ends, but not in between expressed gene torso (tor ). Torso encodes a transmembrane receptor that is activated by substances in the egg shell. The maternal Bcd protein switches the hb gene in the anterior half of the body, so that two sharply halves arise ( all-or -nothing response ). BCD simultaneously suppresses the transcription of CAD, so that the CAD protein found only in the rear half of the body. The other form gap genes in a similar manner from one or two strips at different points of the embryo. So Kr is produced mainly in a region near the center line by activating of Bcd, but repressed by Hb ( prevented) is. Kni is expressed by a mechanism similar to the front end and in a strip in the rear section.

The different body portions are generally characterized by one or a combination of two gap proteins. The gap proteins usually show a maximum rising and falling behind concentrations whose regions overlap more or less wide.

Pair rule genes

The embryonic strips, which are determined by the gap genes are specified respectively by various combinations of pair rule genes. The pair rule genes even ( eve ) and Fushi tarazu - ( ftz ) are each expressed alternately in seven stripes. Other genes such as Runt and Hairy show similar patterns. The aperiodic stripe pattern of the gap genes is superimposed by a periodic pattern. The concentrations of the pair rule proteins are sharply separated in the final state, depending on the cell layer, they no longer overlap as those of the gap genes. Pair mutations in genes usually result in the loss of each of the second segment, so couple regulating genes control the formation of the even-numbered or odd-numbered segments.

Segment polarity genes

The segment polarity genes set both the final sequence of the (para- ) segments as well as their polarity, ie their front and rear end, fixed. The Segmentpolaritätsgen Engrailed (s) is expressed in a narrow area close to the front end of fourteen parameters segment strips. Hedgehog ( hh) shows a similar pattern. The gene Wingless ( wn) is, however, active in strips near the rear end of the para segment strips. This pattern divides the seed embryos at strip of similar strips, which are, however, not in synchronism, but generated in sequence. In contrast to the preceding segmentation genes, the segment polarity genes long time remain, in the case of Engrailed to the winged insect ( imago ) active. With the activity of Segementpolaritätsgene segmentation is completed. In the following stages of development, the identity of the various segments will then be further specified. This is primarily the task of the Hox genes. Upon activation of specific Hox genes, the gap genes ( not so, as the later stages of the segmentation cascade are periodically ) directly play a major role.

Occurrence in other segmented animals

The discovered model organism Drosophila basic scheme could be found in later research in fundamentals at all then studied arthropods. The segmentation runs in all types of a regulatory cascade via an articulated by the segment polarity genes in germ band segments, from. The stages of development lying in front, however, are different from other arthropods in detail. This is, for example, because the most arthropods not begin unlike Drosophila, its development with a syncytium. In addition, the segments are not created simultaneously, but formed during ontogenesis in a segment forming zone at the rear end only gradually in very many ways. In the relatively few far unidentified species studied Bicoid could be found (or a homologous gene ) previously only other dipterans ( Diptera ). In other species even maternal genes are involved in the outline, but in detail each other. The genes cad and Nanos ( nos) seem to be involved widespread. Orthologs or homologous genes to most segmentation genes of Drosophila have been found in most arthropods, however, seems their role in detail to each be different. In the arachnids and centipedes, in addition other regulatory patterns were found in addition that are similar to the patterning of the somites in vertebrates.