In Drosophila, a hierarchy of maternal gene activity genes, as well as zygotic activity of gap, pair-rule and segment polarity genes divides the embryo into 14 repeating metameric domains. These metameric segments will become head, thorax or abdomen segments based on activity of Hom-C genes (which include Antennapedia Complex (Antp-C) and Bithorax Complex (Bx-C) genes). Thanks to expression patterns and knockout mutants, the HOX genes have been pinpointed as the vertebrate homologs of the Drosophila Hom-C genes.
Maternal gene activity genes are in the same linear order as the order of the segments they affect. Each gene in the linear array gives a more posterior identity to the segment in which it is expressed. T2 is the phenotypic “ground state” and expression of various genes of the complex in the more posterior region of the embryo shift this phenotype to more posterior one. Removal of Ubx function causes T3 to take on the identiy of the more anterior T2, while elimination of all Bithorax Complex genes causes all segments posterior to T2 to take on T2 identity. Mutations in BxC (as with AntpC) are homeotic, as they result in replacement of one normal body part with another normal body part, as with UbX mutants having halteres replaced by wings.
The anterior and posterior poles of the Drosophila syncital embryo are established by morphogen gradients of bicoid and nanos protein. Bicoid and nanos are maternal effect genes.
Bicoid (transcription factor)
Bicoid mRNA is present in the egg at the anterior tip, detected by in situ hybridization. Localized maternal bicoid mRNA is translated after fertilization to form a syncitial morphogen gradient of bicoid protein, detected by antibody staining. Bicoid protein diffuses freely to form a morphogen gradient within the syncitial blastoderm. Bicoid and hunchback gradients together divide the embryo into broad strips of expression of gap genes.
- High [bicoid] activates transcription of head gap genes.
- Intermediate [bicoid] activates hunchback transcription.
- Low [bicoid] represses hunchback transcription.
Nanos (translation repressor)
Nanos mRNA is present in the egg at the posterior tip. Localized maternal nanos mRNA is translated into a syncitial morphogen gradient of nanos protein. Nanos protein inhibits translation of hunchback, whose mRNA is evenly distributed throughout the cell. Hunchback represses Kruppel transcription, so nanos' activity causes posterior expression of Kruppel.
Hunchback mRNA is evenly distributed in the cell and, as seen above, hunchback is abundant at intermediate bicoid concentrations (thus reducing kruppel levels) and repressed at low bicoid concentrations (thus increasing Kruppel levels).
Torso RTK (receptor)
A morphogen gradient of activated Torso RTK (receptor tyrosine kinase) at the terminal system (at the tip of each end) de-represses the tailless and huckebein trainscription factors. Tailless patterns the posterior gut primordium as well as the acron and brain.
|Tolloid||Tld||Xolloid||Cleaves Sog, increase concentration of Dpp.|
|Sog||Chordin||Keeps Dpp from binding its receptor, leads to decrease of Dpp concentration.|
|Spaetzle||Protolytic enzymes break off membrane-bound spaetzle, forming spaetzle fragments that float in perivitelline space.|
|Toll Receptor||The spaetzle fragments bind a Toll receptor on the membrane of the syncitial Drosophila embryo.|
|Pelle-Tube||Toll receptor activates pelle-tube complex, which dephosphorylates cactus of the cytoplasmic dorsal-cactus complex.|
|Cactus||Dephosphorylated cactus breaks off and degrades, freeing dorsal to enter the nuclei.|
|Dorsal||This establishes a gradient of nucleic dorsal highest at the ventral region. The dorsal-ventral axis is thus formed. Dorsal is a transcription factor that represses Dpp transcription and activates Twist transcription. Thus, if dorsal is in all nuclei then the embryo is ventralized.|
|Dpp||Nuclei with none or low amounts of dorsal (meaning, the dorsal region nuclei) begin to express Dpp.|
|Twist||The few nuclei with the highest levels of dorsal (meaning, the ventral region nuclei) begin to express twist.|
A/P and D/V axes
Integrating the dorsal-ventral and anterior-posterior axes.
Gurken is a secreted protein. Torpedo is its receptor. Gurken signaling integrates the dorsal-ventral and anterior-posterior axes in Drosophila. Via early gurken signaling, bicoid and nanos at the anterior and posterior induce microtubule formation from each and that extends to the other end. In late gurken signaling, gurken binds and dorsalizes EGFR-expressing follicle cells. Thus, gurken is involved in both anterior-posterior and dorsal-ventral axis formation.