Developmental cascade of morphogens Define Drosophila Body Plan
Imaginal discs and what they teach us about morphogens [email protected].
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Transcript of Imaginal discs and what they teach us about morphogens [email protected].
Imaginal discs and what they teach us about morphogens
wingless
hedgehog/engrailed
* after several hours of interdependence of wingless and hedgehog:situation changes.Development is a timed process; once a situation is established. Nextone is set up…
* engrailed expression is permanent in posterior compartment cells
time
Wingless/engrailed
Where do adult fly structures come from?
Imaginal discs metamorphose intoadult structures in pupal stage
Each part of body grows and develops independently
Each part of the adult fly is derivedfrom an imaginal (imago=adult) disc.
Where do imaginal (derived from the imago=adult) discs come from?
Each disc is derived from set of ectodermal cells inearly embryo.
During metamorphosis The flat sheets of cells, shoot out to from3-D structure.
wingless and hedgehog/engrailed and intersection with:
Step 1: what gene activities “control” where discs are going to form?
wingless expression
A P
decapentaplegic expressiondorsal-ventral restricted stripe
in dorsal ventral axis: dpp
distallessexpression
Step 2: molecules that set up the patterning within disc
segment
posterior
dorsal
ventral
hedgehog
engraile
d
Disc derived from intersection ofwingless/hedgehog and dppexpression (these activatedistalless).
“mature”disc
Expression of these genes ismaintained and drives patterning
wingless
dpp
Expression of dpp and wingless is maintained byhedgehog signalling
Stable boundary from embryos (compartmentboundary): forms the source of morphogeneticmolecules.
“mature”leg disc
Patterning in anterior-posterior axis:
Hedgehog, Wingless, decapentaplegic
Their signalling drives cells into particular differentiation pathways.
17
“mature”leg disc
Intersection of dpp/wingless:
In a body part sticking out: proximal-distal axis…?Intersection between dorsal-ventraland anterior-posterior defines proximal-distal axis!
High point is most distal!
In fact, dorsal ventral boundary was alreadythere in embryos (cells see either green orpink or combinations of these).
Distalless expression defines limb extremities
What is a morphogen I: The “classic” definition by Lewis Wolpert
• A morphogen is a diffusible molecule that elicits direct long-range concentration-dependent changes in gene expression and (in the end) in cellular behaviour.
• Seductive idea because: it provides a simple correlation between specific substances (morphogens), an input (their concentration) and an output (the response of the cells, which is expressed as a developmental pattern).
What is a morphogen II The key attributes of morphogens — on the basis of the classical definition and on present perceptions — are:
• They are secreted, diffusible molecules that come to be distributed in a concentration gradient from a fixed spatial source.
• They generate several (at least three) discrete cellular states in response to different thresholds of the concentration gradient. These cell states are usually associated with differential gene expression.
• They are instructive (that is, they function as a determinant of the cell state) in a direct manner (that is, without intermediates; the response of the cells does not depend on the cell changing states first).
• Examples of molecules and situations that fulfil the criteria above are: Spatzle, specifying the dorsoventral axis of the Drosophila melanogaster embryo. Bicoid, specifying the anterior-posterior axis of the Drosophila embryo
• Activins, specifying and patterning the mesoderm during the early development of amphibians and other vertebrates.
• Sonic Hedgehog, in vertebrate limb development
22
A patterning activity presentin posterior cells
Works as morphogenin anterior-posterior axis
Development of vertebratelimb:naïve group of cells
What is a morphogen III: Sonic Hedgehog in vertebrates
wingless
hedgehog/engrailed
• Uniform overexpression of wingless: modest expansion of engrailed
time
Wingless as a “classic” case of a morphogen (or?)
time
Set up by pair rule
wingless
hedgehog/engrailed
Ubiquitous wingless
Engrailed is expressed only in competent cells
In pupae, discs turn into structures (by extension mainly), cells have a “molecular definition”.
* Can we use development of fly wings/legs as a model for “making” an extremity (understand the underlying genes)?
* Study molecular basis of disc patterning….
Fate map
* Study morphogens….
Zecca M, Basler K & Struhl G Direct and Long-Range Action of a Wingless Morphogen Gradient, Cell, Volume 87, Issue 5, 1996, 833 - 844
UAS FRT CD2, y+ FRT Wgtag
FLP
UAS
CD2, y+
Wgtag
GAL4
GAL4
Clone induction at 1st instar Observation at 3rd instar
THE FLP-out technique
Zecca M, Basler K & Struhl G Direct and Long-Range Action of a Wingless Morphogen Gradient, Cell, Volume 87, Issue 5, 1996, 833 - 844
C Alexandre et al. Nature 505, 180-185 (2014) doi:10.1038/nature12879
Characterization of membrane-tethered Wingless expressedfrom the wingless locus.
Gene expression in wingless-null mutant patches surroundedby wild-type or Neurotactin–Wingless-expressing cells.
C Alexandre et al. Nature 505, 180-185 (2014) doi:10.1038/nature12879
Activity of the wingless promoter in the prospective wing.
C Alexandre et al. Nature 505, 180-185 (2014) doi:10.1038/nature12879
Tissue-specific allele switching to assess the contribution of Wingless release to organ-autonomous growth rate and organismal developmental timing.
C Alexandre et al. Nature 505, 180-185 (2014) doi:10.1038/nature12879
No long range function for Wingless
• Since Wg does not act at a distance then it is not a morphogen with the classical sense of the definition. An idea that held gospel status in developmental biology. Time to revisit Wnts? Tear up the textbooks?
• Or as a famous victorian lady commented on Darwinism: “Let’s hope that it is not true but, if it is true let us make sure that it is not widely known”