Krüppel

Krüppel is a gap gene in ''Drosophila melanogaster'', 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 genes. ''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 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 encode morphogens 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 a transcription factor, and has been shown to act as a repressor. 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’s 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 the pluripotent state of embryonic stem cells.

See also

* ''Drosophila melanogaster''
* ''Drosophila'' embryogenesis
* Maternal effect

References

External links

Diagram
at Davidson College - 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