Lecture Notes

Regeneration
Learning objective:

1. Learn the 4 different mechanisms of regeneration + examples
2. Why mammalian and avian cannot regenerate their CNS

What is regeneration?

 It is the reactivation of development in postembryonic life to restore missing tissue
 Why can salamander grow back limbs but humans cannot?

There are 4 different ways by which regeneration can occur

Can have combination of different modes

1. Stem cell-mediated regeneration
- E.g. regrowth of hair
- Replacement of blood cells
- Present in humans
2. Epimorphosis
- Dedifferentiation of adult structures to form undifferentiated mass of cells that then become respecified
- E.g. regeneration of salamander limbs
- Blasteme forms
- Some definition just say that cell proliferation occurs not necessarily the formation of blastemal
- Examples given for this lecture is blastemal formation.
Blastemal = mass of cells capable of growth and regeneration into organs and body parts
- Dedifferentiate = cell or tissue undergo a reversal of differentiation and lose specialised characteristics
3. Morphallaxis
- Regeneration occurs through repatterning of existing tissue with little new growth
- E.g. hydra
- Not associated with cell proliferation
4. Compensatory regeneration
-differentiated cells divide but maintain their differentiated functions
- e.g. mammalian liver
Occurs in humans

1. Stem cell-mediated regeneration
 (Embryonic) Stem cells can proliferate, creating more stem cells (self-renewal)
 Stem cells can give rise to more differentiated cellular progeny by asymmetric cell divisions
 Adult stem cells are populations of embryonic stem cells which have been retained

Difference between adult and embryonic stem cells

 Embryonic stem cells
- Stem cells derived from undifferentiated inner mass cells of a human embryo
- Pluripotent, meaning able to grow (i.e. differentiate) into all derivatives of the 3 primary germ layers: ectoderm,
endoderm, mesoderm.

During organisms life adult stem cell continuously produce more stem cells but also cells that differentiate

 Blood cells
 Intestinal cells
 Epidermal cells Continuously replenished
 Sperm cells in males
 Injury and environmental factors can cause the production of enormous number of cells
- E.g. RBC when body suffers from hypoxia
- Hypoxia = deficiency in amount of oxygen reaching tissues

, Hematopoietic stem cells are derived from 3 embryonic regions

 Hematopoietic are stem cells that give rise to all other blood cells through a process of haematopoiesis. They are
derived from mesoderm and located in the red bone marrow, which is contained in the core of most bones.
 HSCs from all 3 sources (yolk sac, AGM, placenta) migrate to fatal liver and at time of birth are found in the bone
marrow.
 The bone marrow presents the stem cell niche
 AGM= aorta-gonas-mesonephos region (lateral plate mesoderm near aorta)




Osteoblasts from the stem cell niche sends signal to HSC to maintained their stem cells throughout life

 Osteoblast signal to the HSCs by activating 3 signal transduction pathway:
1. Notch
2. Wnt
3. Receptor tyrosine kinase
 Osteoblast = cell secretes the substance of bone
 Endosteal = vascular membrane of connective tissue that lines inner surface of bonny tissue that forms the medullary
cavity of long bones.
 HSC has receptors for all the 3 signal transduction pathway
 Frizzled receptor mentioned in drosophila segmentation
 Notch is another vital signal transduction pathway in development and functions in neurogenesis (formation of neurons
from neural stem cells)
 Receptor tyrosine kinase is important in the development of a nervous system
 The 3 signalling pathways tell the HSC to maintain stem cell fate