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Schematic of factors in regeneration competent and incompetent limb

Research by Can Aztekin with the Gurdon and Simons labs has provided new insight into why the innate regenerative capacity of Xenopus laevis tadpole limbs becomes suppressed during later stages of development.

 

Secreted inhibitors drive the loss of regeneration competence in Xenopus limbs

Aztekin C et al. (2021) Development dev.199158. DOI: 10.1242/dev.199158.

 

Summary from the paper

Absence of a specialized wound epidermis is hypothesized to block limb regeneration in higher vertebrates. However, the factors preventing its formation in regeneration-incompetent animals are poorly understood.

To characterize the endogenous molecular and cellular regulators of specialized wound epidermis formation in Xenopus laevis tadpoles, and the loss of their regeneration-competency during development, we used single-cell transcriptomics and ex vivo regenerating limb cultures. Transcriptomic analysis revealed that the specialized wound epidermis is not a novel cell state, but a re-deployment of the apical-ectodermal-ridge (AER) program underlying limb development.

Enrichment of secreted inhibitory factors, including Noggin, a morphogen expressed in developing cartilage/bone progenitor cells, are identified as key inhibitors of AER cell formation in regeneration-incompetent tadpoles. These factors can be overridden by Fgf10, which operates upstream of Noggin and blocks chondrogenesis.

These results indicate that manipulation of the extracellular environment and/or chondrogenesis may provide a strategy to restore regeneration potential in higher vertebrates.

 

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Read about earlier published results from this research project on limb regeneration.

Read more about research in the Gurdon and Simons labs.

Watch John Gurdon and Ben Simons talk about their research on YouTube.

 

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The Gurdon Institute reopened on Monday 15th June. Many staff will continue to work from home, and all staff may be contacted by email.

Studying development to understand disease

The Gurdon Institute is funded by Wellcome and Cancer Research UK to study the biology of development, and how normal growth and maintenance go wrong in cancer and other diseases.
 

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