BIOL 303 Lecture Notes - Lecture 3: Apical Ectodermal Ridge, Blastema, Bone Morphogenetic Protein 7
14 May 2018
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Biol 303 April 3rd
Regeneration
• Two types of regeneration
• Morphallaxis: it only involves re-patterning and no growth/proliferation, Ex. one Hydra
gives rise to two smaller Hydra if cut in half
• Epimorphosis: if you cut on the distal side → the tissue rapidly migrated to cover the
exposed surface → formation of a cone-like structure (blastema) → the structure keeps
growing and the tissues undergo proliferation and differentiation → 70 days after
amputation you have regeneration of the entire limb
• Proximal side: also have complete regeneration after 70 days
How does the regeneration occur in salamanders?
• Axolotl AKA Mexican salamander → has a great ability to regenerate limbs and internal
organs
• The apical epithelial cap (AEC) forms at the area where amputation happened
• The tissues beneath the AEC undergo a process called de-differentiation → this tissue is
called blastema
• Tissues in the blastema undergo very rapid cell division, driving the growth of he
regeneration limb → pattern formation and cell differentiation eventually occur
• AEC = an epithelial structure that is functionally analogous to the AER (apical ectodermal
ridge) in limb development
• The AEC can produce FGF family proteins Ex. FGF4 and FGF3 → they promote the
outgrowth of the regenerating limb
• Blastema: a mass of undifferentiated cells beneath the AEC that will give rise to the
regenerated limb
De-differentiation
• Cartilage, muscle, and dermis cells become de-differentiated then they re-differentiate
• Are they multipotent or lineage restricted after they de-differentiate?
• For the cartilage, muscle, Schwann cells, and epidermis, they stay the same cell type
• For the dermis, it can become dermis or cartilage in the regenerated limb
• There is some evidence that the cartilage may become dermis, but it is not strong
• Thrombin: a protease in the serum (blood) of Axolotl → it is important in promoting de-
differentiation
Thrombin Action
• Thrombin induces the cleavage of BMP4 and BMP7 in the serum
• Fragments of BMP4 and BMP7 are more highly active than the un-cleaved versions
• The cleaved versions promote de-differentiation of myotubes into myoblasts
• Myoblasts will later differentiate again to become muscle
Experiment: AG protein
find more resources at oneclass.com
find more resources at oneclass.com
Document Summary
Fgf4 and fgf3 they promote the outgrowth of the regenerating limb: blastema: a mass of undifferentiated cells beneath the aec that will give rise to the regenerated limb. Experiment: ag protein: ag is a nerve-derived protein (from schwann cells) in the control of amphibian limb regeneration. If you cut/remove the nerve before amputation, there is no regeneration of the amputated limb this tells us that you need the nerve to have limb regeneration. In regular limbs, ag comes from the nerve but with aneurogenic animals, ag comes from the limb itself. Retinoic acid: may specify proximo-distal positional value. In humans, they undergo ~60 cell divisions, corresponding to 120 years senescence. If a mutation directly hits a dna repair enzyme = (cid:271)ad, (cid:272)a(cid:374)"t repair other da(cid:373)age. Rodent experiments: calorie restriction: fed food that has a 25-50% calorie reduction without essential nutrient deficiency they had extended life span by up to 50% delayed onset of again.
