Deutsch
TU Dresden

search

Animal Models of Regeneration - Previous and Current Research

Fig. 1: Connective tissue cells (expressing GFP, in green) are carriers of positional information in a regenerating limb. In this 10 day blastema of the upper arm, connective tissue-derived cells express the transcription factor MEIS (in red), which is associated with upper arm identity. Nuclei are marked in blue. Scale 1mm.

Fig. 2: An image of an engineered spinal cord tissue produced from mouse embryonic stem cells. Nuclei are marked blue. These organoids reconstitute local formation of the floorplate expressing sonic hedgehog (green) which induces motor neuron precursors (red), and interneuron neuron precursors (white) to form in the correct location.

Unraveling the molecular cell biology of limb and spinal cord regeneration
Salamanders have the remarkable capability to regenerate their limbs and spinal cords.  Our group has identified the stem cells responsible for this complex regeneration, and the injury-responsive signals that initiate their proliferation.  We have also identified signals that guide the regeneration process to form a faithfully constructed organ with the right types of cells at the right time.  We have recently identified a factor that is released from the epidermis that first forms after the injury.  In addition, we found that in the salamander spinal cord, adult type neural stem cells dedifferentiate to an embryonic type neural stem cell in order to grow the new spinal cord.  This process involves the upregulation of molecular factors involved in planar cell polarity signalling that ensure that the neural stem cells not only divide in the correct orientation, but cause them to self-renew at the early stages of regeneration.  We are now starting to study why the regeneration process happens in salamanders but why it ceases to work in frogs after metamorphosis, and why it only occurs in the fingertip of the mouse by focusing on bone progenitor cells in these different species.

Translation of regeneration lessons to 3D spinal cord organ formation and retinal function in mouse and man
A key feature of successful regeneration is the formation of a tissue that is patterned in three dimensions.  Based on this concept, we have engineered fully patterned three dimensional spinal cord tissue from mouse embryonic stem cells, and retinal tissue from human embryonic stem cells.  Interestingly, global addition of retinoic acid to the mouse spinal cord organoid system causes a spontaneous self-patterning event to give rise to the different neuronal cell types in the right spatial order.  We are actively studying how retinoic acid can confirm this self-organizational ability to the spinal cord organoids.  In contrast in the human system, we have directed human embryonic stem cells to form retinal tissues including the pigmented retinal epithelium (RPE).  We are currently using these cells to screen for potential drugs that could ameliorate defects in RPE cells that are known to cause progressive blindness.

back