Establishing gap gene expression
Bicoid regulates multiple gap genes in a concentration dependent manner. In this way, the Bicoid concentration gradient is transformed into a spatial pattern. A gene X may be active only at high concentrations of Bicoid, whereas gene Y, which has a stronger binding site, is active also at lower concentrations, and therefore at greater distance from the source. Manipulating the concentration of Bicoid in the embryo by genetic means leads to a complete shift of embryonic cell fates anteriorly (in case of decreased bicoid concentration) or posteriorly (in case of an increase). Today we know that these fate shifts are not exactly proportional to the variation in local concentration. Other factors play additional roles in target gene regulation.

Gap genes are regulated by maternal genes, which also feed upon each other.

Bicoid is a transcription factor; it binds to DNA and regulates downstream genes in the anterior region of the embryo, like the zygotic hunchback and the anterior giant domain. Further anterior genes under the control of bicoid are orthodenticle, buttonhead and empty spiracles (not shown here). In addition, Bicoid can also act as a translational repressor of maternal caudal RNA. Whereas caudal RNA is ubiquitously distributed in the early embryo, Caudal protein is restricted to a posterior gradient inverse to the bicoid protein distribution.

This double function of Bicoid is carried out by two different proteins for the posterior system: Nanos is a translational regulator and represses the translation of maternal hunchback mRNA in conjunction with the gene product of pumilio, thereby restricting Hunchback protein distribution to the anterior region of the embryo. Caudal protein acts as a transcription factor to regulate gap gene expression.

Hunchback is a transcription factor and assists bicoid in the regulation of anterior zygotic genes. The expression of Krüppel for example requires both the presence of hunchback and bicoid.

In the absence of nanos, Hunchback protein becomes uniformly distributed throughout the egg. The ectopic presence of Hunchback protein in the posterior part of the embryo represses the expression of knirps and the posterior giant domain. This shows that hunchback can act as a repressor of posterior gap genes. This role of hunchback in keeping the anterior half of the embryo void of posterior gene expression can also be observed in embryos lacking the maternal and zygotic hunchback contribution (not shown here).

The posterior gap genes are activated by both bicoid and caudal. The effect of bicoid on the expression of posterior genes is very weak, whereas the absence of caudal leads to a considerable reduction in the expression of knirps and the posterior giant domain, for example. In the absence of both bicoid and caudal, posterior gap genes are completely abolished.

The terminal gap genes tailless and huckebein (not shown here) are activated by the terminal maternal system.


Media list
Morphogen gradient
 Establishing gap gene expression beginners..........additional information
Establishing gap gene expression advanced..........additional information

Genes discussed
Gene
Gene product - Domains
Function
Links
bicoid (bcd)
transcription factor - homeodomain
maternally provided morphogen involved in anterior patterning of the Drosophila embryo
Interactive Fly
buttonhead (btd)
transcription factor - zinc finger
transcriptonal activator that regulates the segmentation of the head
Interactive Fly
caudal (cad)
transcription factor - homeodomain
plays a role in establishing the posterior domains of the embryo
Interactive Fly
empty spiracles (ems)
transcription factor - homeodomain
required for head + brain development
Interactive Fly
giant (gt)
transcription factor - basic leucine zipper
gap gene
hunchback (hb)

transcription factor - zinc finger
gap gene, later required for proper temporal generation of NB sublineages
Interactive Fly
knirps (kni)
transcription factor - steroid receptor - zinc finger
gap gene, later organizes the development of the second wing vein
Krüppel (Kr)
transcription factor - zinc finger transcriptional repressor
gap gene, later required for proper temporal generation of NB sublineages
nanos (nos)
translational repressor - zinc finger
targets Hunchback- and Bicoid-mRNAs to achieve posterior identity
Interactive Fly
orthodenticle (otd)
transcription factor - homeodomain - paired-like
acts in a combinatorial fashion with the cephalic gap genes empty spiracles and buttonhead to assign segmental identities in the head and brain
Interactive Fly
pumilio (pum) novel posterior group gene binds and regulates Hunchback mRNA Interactive Fly