lecture 9 Flashcards
what are the 2 organisers that pattern the limb in the Ap axis and the PD axis?
for AP axis: the ZPA (zone of polarizing activity) produces FGF4/8 (as morphogens)
for DV axis: the apical ectodermal ridge produces Shh
what are the 2 components of an early bud?
1) core of mesenchymal cells
- cells derived from the lateral plate mesoderm = skeleton and other connective tissues
- cells derived from somites that give rise to muscles and vasculature
2) the outer layer of epithelial cells derived from ectoderm
how is the limb bud development initiated?
along the tip of each limb bud runs a thickened ridge of ectoderm called the apical ectodermal ridge (it is basically an organiser; it disappears as soon as all the basic elements of the limb are in place
mesenchymal cells are now undifferentiated due to the ridge and they start proliferating at distal end of bud; they make cartilage and bones by CONDENSATION
what determines the AP polarity of limbs?
a combinatorial Hox code determines position by activating limb regions and repressing interlimb regions
FORELIMB: Hox - Tbx5
HINDLIMB: Hox - Pitx1 - Tbx4 (Islet1 is required for Tbx4 expression)
Subgroup-5 Hox - anterior forelimb
Subgroup-9 Hox - posterior forelimb
The AP polarity is also determined by the zonal of polarising activity = ZPA
ZPA expresses Shh (it is secreted by the posterior part) and its expressed at the anterior margin of the limb bud; its expression is also maintained by FGF: cells always proliferate from anterior to posterior end
what other factors does AER contain?
FGF8 throughout apical ridge (direction - chemoattractant = attracts cells in the correct direction)
FGF4 and 2 other FGFs in posterior region (define velocity of movement)
how is the proximo-distal axis maintained?
It is maintained by Wnt and FGFs: cells that leave this region differentiate and form limb structure
how do cells know their positional value along the PD axis?
TIME MODEL: cells that are proximal know what to become by the amount of time they spend at the tip of the bud, called PROGRESS ZONE which contains undifferentiated cells; the more time they spend in this zone, the more distal they become
GRADED SIGNALING: use of 2 morphogens
- one coming from the proximal part of the body
- one coming from the distal end - cells interpret these signals and know where to position themselves
these 2 morphogens are:
- retinoic acid coming from the body wall that defines proximal cells
- FGF coming from the apical ectodermal ridge that defines distal cells
how is the DV axis specified?
it is specified by the ectoderm of the bud;
Wnt7a is the gene that ensures that a certain part is dorsal = dorsalizing factor
En1 (engrailed) is the ventralizing factor: it basically represses Wnt7a
what are the differences of limb development between insects and vertebrates?
insects: wings develop from double-layered epithelial cells
vertebrates: limbs develop from mesenchymal cells surrounded by ectoderm
what does the turing network model states?
morphogens repress morphogens in cells next to them, resulting in formation of stripes in zebra for example
this is basically based on a diffusion reaction of morphogens
