Biology 3338A Lecture Notes - Lecture 14: Zone Of Polarizing Activity, Mesenchymal Stem Cell, Wild Type
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24 Jan 2015
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Vertebrate Limb Development Gilbert 485-510
-complex but highly conserved patterns
13.1, .3
3 axes
-proximal-distal (shoulder-fingertip)
-anterior-posterior (thumb-little finger)
-dorsal-ventral (knuckles-palm)
plus neural crest !
Limbs (limb buds) only grow at limb fields
-4 limbs in vertebrates - 2 pairs opposite
each other
-position constant with respect to Hox gene
expression
Hox expression in fly and mouse -there are several Hox paralogue groups,
Hox a, b,
c and d
SLIDE 1
SLIDE 2
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Hox expression is, in part, controlled by retinoic acid gradients
“limb field”
Developmental anomalies caused by thalidomide.
DNA binding teratogen.
Many temporal effects including;
altering (lowering) integrin expression.
altering IGF signalling.
Thalidomide was a drug given to pregnant women for nausea
So 50s and 60s women gave birth to children with limb problems
Don’t memorize this stuff
Depending on when women takes thalidomide depends on what is missing- could be ear, leg
This is because timing of things is very precise
Once established, you cant go back
SLIDE 3
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Hox expression is, in part, controlled by retinoic acid gradients
“limb field”
Limb buds form from lateral plate (skeletal) and somitic (muscle) mesoderm
-prospective limb mesenchyme (from lateral plate meso) expresses FGF-10
-ectopic FGF-10 can induce extra limb buds 13.5
Limbs are put in limb buds
These locations are in response to hox gene and retinoic acid
First, you see exression of FGF-10 from lateral plate mesoderm
Chick embryo does not have limb buds yet but there is expression of FGF-10 (because of hox gene expression and retinoic acid)
FGF-10 turns on in limb buds
If FGF10 is put in different location, there can be extra limbs growing because it drives limb bud development
Depending on amount of retinoic acid because of a gradient, different structures will form