Segmentation Flashcards
What is the main embryo D-V morphogen?
It is called dorsal. It determines the ventral face.
What kind of protein is dorsal?
It is a transcription factor like the other morphogens.
How is dorsal distributed in the embryo?
mRNA and protein are both evenly distributed throughout the embryo.
How is a gradient of dorsal established?
The amount of active dorsal determines which side is active.
It is sequestered in the cytoplasm of the dorsal side by a protein called cactus.
What does the dorsal gene do?
On ventral side of the embryo it enters the nucleus and activates production of dorsal protein.
The gradient of dorsal TF creates a gradient of spatzle and Toll gene products on the ventral side.
What do spatze and Toll do on the ventral side of the embryo?
They trigger a signal transduction pathway in cells that releases dorsal, migrates to nucleus, and activates genes for ventral fates.
How is dorsal activated?
dorsal is inactivated by cactus. TOLL on embryo surface binds to SPZ ligand which phosphorylates cactus and releases dorsal allowing it to move to the nucleus.
Dorsal activates transcription of zygotic ventral patterning genes.
On dorsal side the dorsal stays attached to cactus.
What is the pathway of dorsal release from cactus?
SPZ ligand binds to TOLL.
TOLL activates PLL which phosphorylates CACT-DL releasing DL and this results in DL exerting its effect in the nucleus.
CACT = cactus
DL = dorsal
What happens if TOLL is mutated?
There is no way to release dorsal from cactus and so there will be no entry of any dorsal into any nucleus.
What happens if cactus is mutated?
There is an inability for dorsal to be held away from the nucleus by cactus and so that results in all cells having dorsal expression both ventrally and dorsally.
What does dorsal do in the nucleus?
It leads to mesoderm production most ventrally and then ectoderm deeper to it.
I.e it leads to localisation of activity.
What are the first zygotic A-P genes released?
gap genes.
Kruppel and knirps (mutants have gaps in normal segmentation) promoters have differential sensitivity to the maternally derived TFs like bicoid, HB-M, and Caudal.
What are the targets of gap genes?
There is a bifurcation of function:
One branch establishes correct number of segments
Another branch assigns proper identity to each segment.
What do kruppel and knirps genes do?
They are important for large numbers of segments to be produced.
How are the pair-rule genes activated?
By the gap genes and they are responsible for the production of stripes of segmentation. (on-off, on-off, etc)
What do segment polarity genes do?
They create defined borders between segments by defining anterior and posterior aspects of each segment.
What is the hierarchy of segmentation?
Starts with gap genes -> Pair-rule genes -> Segmentation polarity -> Specialisation by homeobox/homeotic genes.
How are gap genes activated?
They are the first zygotic genes to be expressed along A-P axis.
Mother sets up gradient of bicoid mRNA. Bicoid activates HB-zygotic which activates giant, kruppel, and knirps.
What does kruppel respond mostly to?
High levels of HunchBack in a concentration-dependent manner.
High levels of HB in anterior suppress kruppel.
Intermediate levels of HB activate kruppel.
Low levels of HB fail to activate kruppel.
So kruppel is most active in the middle. hence the segmentation they produce.
What do pair-rule genes do?
Expressed in alternating bands resulting in zebra like pattern that divides the embryo into 15 subunits.
What pair-rule genes are expressed?
3 primary pair rule genes: hairy, even-skipped, and runt.
5 secondary genes. (including fushi tarazu)
What do Hedgehog genes do?
Allow for differentiation between left and right sides of the body.
How are homeotic selector genes regulated?
The pair-rule and gap genes interact to regulate the homeotic selector genes.
What do homeotic genes do?
Encode TFs and control segment identity
How do homeotic selector genes regulate other genes?
All the homeotic selector genes contain the homeobox domain.
Homeodomain allows TF to bind DNA.
Proteins containing homeodomains may be activators or repressors of transcription.
How many hom/hox gene clusters are there in flies and humans?
Flies: 1 cluster in insects
Humans: 4 Hox clusters in mammals.
