• campus:  a to z index
• map
• directory
• calendar

Search:

Shannon Odelberg

Assistant Professor of Neurobiology and Anatomy and of Internal Medicine

B.S. Weber State University

Ph.D. Virginia Commonwealth University

Research

References

odelberg@genetics.utah.edu

Shannon Odelberg's Lab Page

Shannon Odelberg's PubMed Literature Search

Research

Newts have the remarkable ability to regenerate several anatomical structures and organs including their limbs, spinal cords, hearts, tails, retinas, lenses, optic nerves, intestines, jaws, and parts of the brain. Many of the progenitor cells required for regeneration are created de novo by the dedifferentiation of mature cells located near the site of injury. This degree of cellular plasticity is unique to organisms with marked regenerative abilities and is not observed in mammals. My laboratory is interested in identifying the genes that regulate cellular plasticity with the hope of someday applying this knowledge to enhance the regenerative capacity in mammals.

We have found that proteins present in regenerating newt limbs, but absent in intact limbs, can induce both newt and mouse myotubes to dedifferentiate. These results indicate that the intracellular signaling pathways controlling dedifferentiation are intact in at least some mammalian cells and suggest that the lack of cellular plasticity in mammals may be due to the absence of extracellular signals capable of initiating the dedifferentiation process. In an effort to identify these extracellular signals, we have performed differential expression analyses between regenerating and intact newt limbs and have cloned the full-length open reading frames of more than 130 upregulated genes.

Based on this initial screen, we have focused our efforts on two classes of extracellular proteins that are excellent candidates for initiating dedifferentiation: 1) matrix metalloproteinases (MMPs) and 2) cytokines. Inhibition of MMP function leads to abnormal limb regenerates, suggesting that MMPs are required for normal limb regeneration. My laboratory is involved in identifying which MMPs are required for limb regeneration and in elucidating the biochemical and cellular mechanisms of MMP function during limb regeneration. We have also identified several putative cytokine genes that are upregulated during the initial stages of limb regeneration, and we are testing these genes for function using cell culture assays. Methods for assessing gene function in vivo are being explored, including inducible transgene expression and knockdown of gene expression in newt limbs.

An adult newt can regenerate its spinal cord following either complete transection or partial ablation. This regenerative ability is thought to be dependent on three factors: 1) the activation of quiescent cells within the spinal cord; 2) efficient axon regrowth across the lesion and subsequent reestablishment of functional synapses; and 3) the absence of a glial scar, which can act as a physical and molecular barrier to axon regrowth. We have shown that several cell types are activated and begin to proliferate following a spinal cord injury. As axons regrow across the lesion, they associate with meningeal and glial cells, which establish a permissive environment for regrowth. Surprisingly, severed newt axons regrow through lesions expressing high levels of matrices that are normally thought to be inhibitory to axon growth, such as chondroitin sulfate proteoglycans. We have identified several candidate genes that are upregulated during newt spinal cord regeneration and might function to activate quiescent cells, promote axon regrowth, or prevent glial scar formation.

 

Newt limb and spinal cord regeneration. Left panel. An adult newt forelimb regenerates in 7-10 weeks following amputation through the stylopod. Right panel. An adult newt can regenerate a completely transected spinal cord and regain function in less than 10 weeks. Arrow indicates lesion site (shown as a gap in the middle photograph) that contains regenerated neural tissue at 10 weeks post-injury.

References