lec 10- segmentation in Drosophila Flashcards
what genes do gap genes activate?
pair-rule genes
what do pair-rule genes define?
para segments
what do the segmentation genes define?
segments into the developing embryo
what are pair-rule genes?
transcription factors
what do pair rule genes divide the embryo into?
repeated stripes just before cellularization
how many bands does one pair-rule gene have?
7
what are the two pair rule genes that create the 14 parasegments in the embryo?
even-skipped and fushi tarazu
after the parasegments are formed, what occurs?
segmentation, pair rule genes activate the transcription of segmentation genes
what are parasegments?
repeating units that form along the AP axis, and are also offset from segments
what does the anterior region of a parasegment line up with?
with the posterior region of one segment and the anterior of the next
does the segmentation pattern carry over into the fly?
yes, resulting in the development of specific appendages like wings or legs which develop on specific segments only
how is each stripe of a pair rule gene regulated?
by different combinations of maternal effect and gap genes
how are pair rule stripes formed?
they form via a combination of gene product accumulation in the stripes and loss in the intervening regions
where are stripes established and how are the inter stripe regions made?
-they are established in areas where gene expression continues or is increased
-while in the inter stripe regions, gene expression is repressed and pre-existing gene products are degraded
how is the expression of even skipped regulated by bicoid, hunchback, giant, and kruppel?
-bicoid and hunchback activate the even skipped gene in a broad domain
-giant and kruppel are repressors which define the boundaries of the even skipped stripe
can giant and kruppel still repress a even skipped stripe when bicoid and hunchback are still present?
yes, they overtake
how are the anterior and posterior portions of the even skipped stripe determined?
-anterior is determined by the threshold concentration of giant gene
-posterior is determined by the threshold concentration of the kruppel gene
what do the regulatory regions of pair rule genes contain?
different modules
what does each module do?
controls gene expression in different regions of the embryo
what does each module have different combinations of binding sites for?
transcription factors
how is the positioning of the stripes determined?
by the binding of activators and repressors to module binding sites
how does gene expression occur with respect to activators?
it occurs when the number of activators are above a threshold concentration
how is transcription stopped with respect to repressors?
binding of repressors above a threshold level prevents transcription
what does the ability of a gene to respond to threshold levels of a transcription factor depend on?
the presence of high and low affinity sites for proteins in that regulatory region
what activates segmentation genes?
pair rule genes
what happens during segmentation?
the positions of parasegment become fixed and the boundaries of the segments that are visible in the larval epidermis become established
what are the bristles on the ventral epidermis called?
denticles
do denticles occur in the posterior region?
no, only in the anterior as stripes
what does the larval denticle pattern depend on?
the correct establishment and maintenance of the embryonic parasegment boundaries
what due mutations in segmentation genes cause?
they alter the denticle pattern in larvae, an example of a mutation is hedgehog which loses the naked region of each segment
what is a compartment?
a region in which all the cells are made up of descendants of cells that were present when the compartment was set up, no other cells present
when parasegments are set up, what do the cells at the anterior form?
a compartment
what do the cells in the parasegment compartment follow?
cell lineage restriction
what is cell lineage restriction?
cells do not move across the boundary into adjacent parasegments
what do the parasegment compartment cells express?
transcription factors called engrailed
what activates the expression of engrailed?
fushi-tarazu and even skipped
what does engrailed do?
changes the properties of cells so they do not mix with the cells of adjacent compartments and it confers a posterior segment identity
are engrailed selector genes?
yes
what is a selector gene?
a gene whose activity causes cells to adopt a particular fate
to maintain the posterior character of segment, what must engrailed do?
be expressed throughout development
which genes control the signals sent between cells that set up parasegment boundaries?
engrailed, hedgehog, wingless
what are hedgehog and wingless genes?
secreted signalling molecules
what establishes the expression of wingless and engrailed in cells?
pair rule genes
what does engrailed activate the expression of ?
hedgehog
where are the engrailed, hedgehog, and wingless genes located in a parasegment?
-engrailed and hedgehog is located at the anterior, engrailed is activated by fushi tarazu and even skipped
-wingless Is located at the posterior, activated by the expression of the pair rule gene sloppy paired and no fushi tarazu or even skipped is present
what are the 4 steps to maintaining segmentation boundaries
- wingless protein is secreted from cells expressing wingless gene and it diffuses to neighbouring cells
- secreted wingless protein signals to the cells expressing engrailed and hedgehog, maintaining their expression in those cells
3.the hedgehog protein is secreted, and diffuses to adjacent cells - hedgehog signals maintain wingless expression in cells at the posterior of the adjacent parasegment
what happens in the Wnt/B-catenin signalling pathway when no Wnt is present?
- B-catenin is bound by a destruction complex of proteins in the cytoplasm
- kinases in the complex phosphorylate B-catenin which targets it for degredation via the proteasome
- with no B-catenin in the nucleus, co-repressors bind to the transcription factors and prevent transcription
what happens in the Wnt/B-catenin signalling pathway when Wnt is present?
- Wnt binds to the receptor frizzled and activates the pathway
- Dishevelled and kinases of the destruction complex are recruited to the receptors where they are prevented from forming B-catenin destruction complex
- B-catenin accumulates and enters the nucleus where it displaces the co-repressors and activates transcription of target genes
what happens in the hedgehog signalling pathway when no hedgehog is present?
- Patched receptor inhibits Smoothened
- When Smoothened is inhibited, it binds to a complex of proteins that includes the transcription factor cubitus interruptus (Ci)
- Ci also forms a complex with another protein in the cytoplasm called suppressor of fused or Su(fu)
- Ci in the complex associated with Smoothened is phosphorylated by several protein kinases
- Phosphorylated Ci is cleaved forming a truncated protein that enters the nucleus and represses hedgehog target genes
what happens in the hedgehog signalling pathway when hedgehog is present?
- The hedgehog receptor Patched no longer inhibits Smoothened
- Ci is released from both complexes
- it enters the nucleus and activates gene transcription
what do the hedgehog signals maintain?
wingless expression in cells at the posterior
what do wingless signals maintain?
engrailed and hedgehog, expression in cells at the anterior
where is the expression of patched located?
on the cells adjacent to the ones that produce hedgehog and engrailed
where is the expression for frizzled (the receptor for wingless) located?
in all the cells
do the hedgehog and wingless signalling molecules diffuse from the cell and form gradients along the AP axis?
yes
what does the gradient formed by hedgehog and wingless provide?
it provides cells with the signals they need to acquire their identities
when the hedgehog, wingless, and engrailed protein signalling pathways are intact what happens? what happens when wingless is missing due to mutation?
-compartment boundary is established
-loss of parasegment boundary due to no expression of hedgehog or engrailed
