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Krüppel is a
Diagram
at
Krüppel is a gap gene
A gap gene is a type of gene involved in the development of the segmented embryos of some arthropods. Gap genes are defined by the effect of a mutation in that gene, which causes the loss of contiguous body segments, resembling a gap in the norm ...
in ''Drosophila melanogaster
''Drosophila melanogaster'' is a species of fly (an insect of the Order (biology), 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", "pomace fly" ...
'', located on the 2R chromosome, which encodes a zinc finger C2H2 transcription factor. Gap genes work together to establish the anterior-posterior segment patterning of the insect through regulation of the transcription factor encoding pair rule genes. These genes in turn regulate segment polarity gene A segmentation gene is a generic term for a gene whose function is to specify tissue pattern in each repeated unit of a segmented organism. Animals are constructed of segments; however, Drosophila segments also contain subdivided compartments. There ...
s. ''Krüppel'' means "cripple" in German, named for the crippled appearance of mutant larvae, who have failed to develop proper thoracic and anterior segments in the abdominal region. Mutants can also have abdominal mirror duplications.
Human homologs
Homologous chromosomes or homologs are a set of one maternal and one paternal chromosome that pair up with each other inside a cell during meiosis. Homologs have the same genes in the same loci, where they provide points along each chromosome th ...
of Krüppel are collectively named ''Krüppel''-like factors, a set of proteins well characterized for their role in carcinogenesis.
''Krüppel'' expression pathway
''Krüppel'' is expressed in the center of the embryo during the cellular blastoderm stage of development. Its expression pattern is restricted to this domain largely through interactions with the maternal effect genes ''Bicoid'' and ''Nanos'', and fellow gap gene ''Hunchback'' and ''Knirps.'' ''Bicoid'' maternal transcripts are deposited at the anterior end of the embryo, while ''Nanos'' maternal transcripts are located at the posterior. ''Hunchback'' mRNA transcripts are present throughout the embryo. ''Bicoid'' and ''Nanos'' both encodemorphogen
A morphogen is a substance whose non-uniform distribution governs the pattern of tissue development in the process of morphogenesis or pattern formation, one of the core processes of developmental biology, establishing positions of the various ...
s that have the opposite effect on ''Hunchback'' mRNA translation – ''Bicoid'' activates translation, whereas ''Nanos'' represses it. As such, ''Hunchback'' mRNA is translated so that ''Hunchback'' protein is present in the concentration gradient which decreases along the anterior – posterior axis. This ''Hunchback'' gradient indirectly results in an anterior boundary for ''Knirps'' expression. Other factors induce a posterior boundary, so that ''Knirps'' is expressed in a stripe in the posterior region of the embryo.
''Hunchback'' and ''Knirps'' are both transcription factors that regulate ''Krüppel'' expression. High levels of ''Hunchback'' inhibit expression, whereas low levels of ''Hunchback'' activate expression. ''Knirps'' acts as a repressor to inhibit expression. This results in ''Krüppel'' being expressed in a stripe in the center of the embryo's A-P axis, where Hunchback concentration has dropped to a low enough level so that it can act as an activator, but ''Knirps'' is not yet present to inhibit.
In this way the initial gradients of morphogens can lead to the establishment of a specific region within the blastoderm.
It can be compared to a narrow bandwidth filter in engineering.
Effects of ''Krüppel'' expression
The ''Krüppel'' protein is atranscription factor
In molecular biology, a transcription factor (TF) (or sequence-specific DNA-binding factor) is a protein that controls the rate of transcription (genetics), transcription of genetics, genetic information from DNA to messenger RNA, by binding t ...
, and has been shown to act as a repressor
In molecular genetics, a repressor is a DNA- or RNA-binding protein that inhibits the expression of one or more genes by binding to the operator or associated silencers. A DNA-binding repressor blocks the attachment of RNA polymerase to the ...
. It functions in collaboration with other gap genes and their localized protein products to regulate the expression of the primary pair rule genes – ''even skipped'' (''eve''), ''hairy'' (''h''), and ''runt.'' It has been postulated that ''Krüppel'' inhibits ''eve'' expression to create the posterior boundary of ''eve'' stripe two, and evidence has also been found for ''Krüppel'' being a player specifically in the formation of ''hairy'' stripe 7. The expression patterns of pair rule gene will in turn regulate the segment polarity genes, making ''Krüppel'' essential for proper development along the anterior posterior axis and segment identity.
Clinical significance
''Krüppel'' has shown homology to the mammalian ''Krüppel''-like factors, which play key biological roles in the pathogenesis of many human diseases: cancer, obesity, inflammatory disorders and cardiovascular complications. Moreover, KLFs are known to be involved in inducible pluripotent stem cells generation, and preservation of thepluripotent
Cell potency is a cell's ability to differentiate into other cell types.
The more cell types a cell can differentiate into, the greater its potency. Potency is also described as the gene activation potential within a cell, which like a continuum ...
state of embryonic stem cell
Embryonic stem cells (ESCs) are Cell potency#Pluripotency, pluripotent stem cells derived from the inner cell mass of a blastocyst, an early-stage pre-Implantation (human embryo), implantation embryo. Human embryos reach the blastocyst stage 4†...
s.
See also
* ''Drosophila melanogaster
''Drosophila melanogaster'' is a species of fly (an insect of the Order (biology), 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", "pomace fly" ...
''
* ''Drosophila'' embryogenesis
* Maternal effect
A maternal effect is a situation where the phenotype of an organism is determined not only by the environment it experiences and its genotype, but also by the environment and genotype of its mother. In genetics, maternal effects occur when an orga ...
References
External links
Diagram
at
Davidson College
Davidson College is a Private college, private Liberal arts colleges in the United States, liberal arts college in Davidson, North Carolina, United States. It was established in 1837 by the Concord Presbytery and named after American Revolutiona ...
- a Drosophila embryo at the cellular blastoderm stage triple-labeled for three segmentation proteins including Krüppel (in blue) Hairy (green) and Giant (red).
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{{DEFAULTSORT:Kruppel
Drosophila melanogaster genes