Development of limbs and fins Flashcards
More notes on this in book
What does the limb consist of?
- skeleton (bone)
- muscle
Where does the musculature of the limb come from?
- comes from the somite
Where does the bone of limb come from?
- mesoderm
Where does the lateral plate mesoderm run?
- runs along the majority of the trunk
Where does the lateral plate mesoderm sit in relation to the somites?
- sits lateral to the somites bilaterally
Where is the forelimb always positioned?
- positioned at the cervical-thoracic boundary
- brachial plexus
Where is the hind limb always positioned?
- at the lumbar sacral boundary
- pelvic plexuses
What happens to knockout mice missing the Hoxb5 gene?
- has mal-positioned forelimbs (more anterior)
What genes are the regulator for positioning of genes?
- Hox genes
With limb positioning there are remarkable consistencies between species but there can be issues - what could these be?
- calf with additional limbs
- frogs with additional pair of limbs
Limbs grow from a specific part of the LPM. They are induced to grow out by what signal?
- fibroblast growth factor 10
When limbs are induced to grow by fibroblast growth factor 10 the tissue grows out to for a bud - what does this bud consist of?
- consists of both ectoderm and mesenchyme
What triggers the tissue to grow out and form a bud?
- within the limb territories there are receptors for fibroblast growth factor and once this is stimulated this will trigger proliferation
What is the apical ectoderm ridge?
- a special ectodermal structure at the apex of the limb bud is called the apical ectodermal ridge (AER)
What does the apical ectodermal ridge control?
- controls the rate of cell proliferation in the underlying mesenchyme (proliferation and differentiation)
What does the outgrowth of the apical ectodermal ridge correspond to?
- to proximo-distal growth
The apical ectodermal ridge maintains genes that control what?
- maintains genes that control patterning of the antero-posterior axis (thumb - little finger)
- maintains genes that control the dorsal ventral axis (back of hand to palm)
In proximal-distal outgrowth of the forelimb what is the most proximal bone?
- the humerus
In the forelimb due to proximal- distal outgrowth what are the middle bones?
- the radius and ulna
In proximal to distal outgrowth what is the most distal bones in the forelimb?
- the digits
What does signals from the AER to the adjacent 200um of the mesoderm tell cells to do in the forelimb?
- become either humerus, radius/ulna or digits
What is the region between the AER and the adjacent 200 um of mesoderm called?
- this region is called the progression zone
The AER is crucial if its removed what will happen?
- proximal to distal limb growth wont happen
Proximo-distal outgrowth is thought to be due to what?
- this is thought to be due to the amount of time mesoderm cells spend in the progress zone
In forelimb proximo-distal outgrowth the cell exiting the progression zone first and last will become the what?
- first = humerus
- last = digits
Combinations of hox gene expression are key in controlling what?
- cell differentiations in the limb
What Hox genes are required to make digits?
- Hoxa 9, 10, 11, 12 and 13
What hox genes are required to make the humerus and femur?
- hoxa9 = humerus
*hoxd9 = femur
What is the anterior-posterior axis?
- this is the thumb to little finger axis
When is the anterio-posterior axis specified and what is this due to?
- in very early development (almost before you can see a limb bud) due to to signals coming from AER
The anterio-posterior axis requires a small piece of tissue situated at the posterior edge of the limb - what is this called?
- the zone of polarising activity (ZPA)
What molecules does the ZPA express (in the anterio-posterior axis)?
- expresses a molecule called sonic hedgehog (Shh)
The sonic the hedgehog molecule is a diffusible molecule, what does this mean for concentration?
- so high concentration at the posterior end and a low concentration at the anterior end
High concentrations of Shh specifies what at the posterior end?
- specifies digit 5 at the posterior end
Low concentration specifies what digit at the anterior end?
- digit 1
What is required for the AER to ensure Shh is expressed in the ZPA?
- fibroblast growth factor (Fgf)
What is the dorso-ventral axis regulated by?
- this is regulated by the ectoderm that covers the limb mesoderm
In the dorso-ventral axis wnt7a is expressed where and induces what?
- expressed in the dorsal side of the ectoderm
- it induces Lmx1 expression in dorsal mesenchyme
In the dorso-ventral axis what gene is expressed on the ventral side?
- engrailed gene
signals from the AER, including Fgfs ensure dorsal and ventral signals are what in the dorsol-ventral axis?
- ensure dorsal and ventral signals are in the correct position
What does the like first look like as it starts growing out?
- starts growing out as a paddle shape
The paddle shape of the limb needs refining to produce a functional skeleton - what days does this take place?
- day 10-14
Where does programmed cell death (apoptosis) occur in the forelimb?
- between the radius and ulna and at the end of the limb and between the digits
Apoptosis between bones in the limb allows for what?
- this removes cells and allows separate skeletal elements to emerge
What are the main group of molecules responsible for the apoptosis to sculpt limbs?
- are the BMP’S = Bone Morphogenetic proteins
Evolution/natural selection doesn’t generate a completely new structure - what does it usually do instead?
- usually it is a modification of structures already present
Do all limbs have the same basic design?
- yes
Fish have fins in different positions - where are the fins located?
- they have dorsal and ventral fins that are unpaired ( likely to be hox genes that encode for this)
- they have paired pectoral and pelvic fins
The duck has a webbed foot - what is this?
- soft tissue persisting between the digits
Developmental studies conducted on the webbed foot found out what about cells death?
- there is no cell death between the digits
- but there is normal cell death in other regions of the limb
What would happen if you place BMP inhibitors in between digits in the developing chick?
- there is no apoptosis so they would have webbed feet
What do changes in expression of BMP and or its inhibitors change?
- change foot morphology
What about snake limbs?
Do they have them?
What can they have?
- the majority if snakes have complete lack of limb develop
- some however, such as pythons have pelvic girdles and rudimentary femurs
What is associated with absence of forelimb?
- changes in Hox gene expression within the LPM
Expansion in the expression of certain Hox genes along the axis of the body can result in what?
- in the majority of the vertebrate being thoracic
What does the lack of a cervical-thoracic boundary result in?
- no specific site therefore for the forelimb to develop
Describe python hindlimb development?
- hindlimb buds do start to form in the python
- the AER however doesn’t form any further
- no AER results in no P-D outgrowth and therefore no ZPA to create an A-P pattern
- this results in the formation of a tiny spur - a very small femur
