Drosophila Axis Development

Overview of Drosophila oocyte
Drosophila development begins in the egg of the female fly. An ovariole is one of the tubes of which the ovaries of most insects are composed. This is where the development of the ooycte begins to form into a fully developing Drosophila egg.

The ovariole structure consists of multiple oocyte/nurse cells complexes (named oogonioum) that undergo duplication without a complete cleavage. This leads to a string of these eggs in sequential level of development.

Formation of the egg
After fertilization, the zygotic nucleus undergoes rapid division within the oogonioum. The term that defines a single cell with multiple nuclei is called syncitium. After the multiple nuclear dividisions a majority of the nuclei head to the outer edge of the egg. At this point, the outer edge nuclei are transformed into follicle cells that surround the egg. This essentially creates a blastoderm (a hollow structure surrounded by cells).

The remaining nuclei in the blastoderm trasform into nurse cells while a single nuclei transforms into an oocyte. The oocyte nucleus remains at the posterior end of the egg chamber. The nurse cells 'feed' the oocyte by delivering cytoplasmic components to the growing oocyte. In early development, microtubules are formed with their positive end towards the posterior of the egg and their negative ends towards the nurse cells.

The follicle cells that surround the egg sack express many receptors. They contact the oocyte through the use of gap junctions. During oocyte maturation, there is secretion of a RNA regulatory factor named '''Gurken. Gurken interacts with the Torpedo''' recptors that are present on the follicle cells.

Anterior/Posterior Development
When Gurken interacts with the Torpedo receptor on the follicle cell it sends a feedback signal to the oocyte. This signal tells the oocyte to re-polarize the microtubules. Repolarization of the microtubles has a profound effect on the development of the anterior/posterior axis of the drosophila egg.

Determination of the A/P axis begins with the transport of Bicord and Oskar mRNA. The Bicord mRNA is transported towards the negative end of the microtubule while Oskar is transported to the positive end. By the end of the initial transport, Bicord is found at high concentration at the anterior end while Oskar is found in high concentration at the posterior end.

The main mRNA seqeunces that are used in the formation of the A/P axis is as follows:
 * 1) Bicord (bcd)
 * 2) Oskar (Osk)
 * 3) Exuper (Exu)
 * 4) Swallow (Swa)
 * 5) Staufen (Stu)
 * 6) Nanos (Nos)
 * 7) Smaug (Smg)
 * 8) Hunchback (Hb)
 * 9) Purmillio (Pum)
 * 10) Krupple (Kr)
 * 11) Knirps (Kni)

AP_axis_chart.png
Remember, localization of Bicord follows the Localization Protection mechanism: where the protein is protected from degradation so long as its able to bind to a protein. This means that Bicord does not fill the entire embyro, rather it creates a gradient with the highest concentration at the anterior end.

The following is the steps in the anterior development:
 * Exu, Swa, Stu -> Bcd
 * 1) Bcd->Hb
 * 2) Bcd->Kr
 * 3) Hb-I Kr

Posterior Development
The following is the mechanism for the development of the posterior end of the egg:
 * 1) Smg-I Nos
 * 2) Osk->Nos
 * 3) Hb-IKni
 * 4) Nos/Pum-I Hb

Dorsal/Ventral Development
The nucleus migrates to dorsal side of the oocyte and causes a build up of Gurkin interacting with Torpedo receptor to inhibit Pipe. The inhibition of pipe allows for the expression of dorsal specific proteins. Gurkin also inhibits Mirror that activates Pipe.

Since Gurkin is localized at the dorsal end of the cell the ventral pipe (glucosyl transferase) is active and initates a protyltic cleavage cascade proteolytic through nudel.

Pipe-->Nudel-->Gastrulation defective-->Snake-->Easter--> Spazle

Spazle actes on a Toll receptor to iniate a homolog pathway to NFkB (Dorsal/dl) and IKB (Cactus)

Spazle-->Toll Receptor--P-->Pelle--P--|Cactus|Dorsal--->nucleus

When Cactus is bound to Dorsal it prevents Dorsals translocation to the nucleus. When Pelle Phosphorylates Cactus, Cactus is marked and degraded allowing Dorsal to relocate to the nucleus. This creates a gradent at the ventral portion of the cell with nuclear Dorsal. Nuclear Dorsal leads to the expression of ventral structures/genes.

dl--|Zen (Zen is very sensitive to inhibition by dl)

dl--| dpp (dpp is less sensitive to dl)

dl-->sog

dl-->twi

dl/twi-->sna

dl/twi-->sina

sna--|sog