[2] This is in contrast to differentiation, where differences in gene expression, morphology, or physiology arise in a cell, making its function increasingly specialized.
[3] The loss of specialization observed in dedifferentiation can be noted through changes in gene expression, physiology, function within the organism, proliferative activity, or morphology.
[4] While Manning's research was about plants, it helped establish the foundation for our modern-day understanding of dedifferentiation and cell plasticity.
Dedifferentiation would be represented by the marble moving uphill through the pathways it has already taken until it settles somewhere above the most downhill location.
[6] For example, MMP,[7] the matrix metalloproteinase, has shown up-regulated activity during early stages of limb regeneration.
MSx1 [2], a gene that is a member of the homeobox [3] family, encodes a transcriptional repressor that can prevent differentiation in epithelial and mesenchymal [4] progenitor cell types.
[9] Across various vertebrate models that have been used to study cell behavior during wound healing, dedifferentiation is consistently reflected by changes in gene expression, morphology, and proliferative activity that distinguish it from its previously terminally differentiated state.
Upon injury, zebrafish cardiomyocytes have been found to have the capability to differentiate and subsequently rapidly proliferate as a wound healing response.
These murine primary myotube cells then exhibited a decrease in differentiated cardiomyocyte gene expression, an increase in proliferation, and a change in morphology.
[15] In this study, the addition of Ras blocks Schwann cell differentiation and induces dedifferentiation.
Adult newts can regenerate limbs, tail, upper and lower jaws, spinal cord, retinas, lenses, optic nerves, intestine, and a portion of its heart ventricle [9] Axolotls share the same abilities, save the retina and lens.
This is different from mammalian regeneration, because mammals use preexisting stem cells to replace lost tissues.
[9] Dedifferentiation in the newt occurs 4–5 days after limb amputation and is characterized by cell cycle re-entry and down-regulation of differentiation markers.
This brief example outlines dedifferentiation in an invertebrate species, and interestingly involves the Msx pathway, as detailed above in the mechanisms section.
Upon amputation, lancelet tails healed and formed a blastema [11] structure, suggesting dedifferentiation of cells to prepare for regeneration [17] Lancelets can regenerate anterior and posterior structures, including neural tube, notochord, fin, and muscle [17] The blastema that is formed expresses PAX3 and PAX7, which is associated with activation of muscle stem cells.
[18] While its definition can be conflated with dedifferentiation, it is more often perceived as a loss of differentiation leading to abnormal cell activity, including but not limited to tumorigenesis.
This implies that the cell is able to adapt to environmental stimuli, and that it is possible to reverse embryological commitments in the form of differentiation.