Embryo insights pave way for muscle and spinal cord stem cell therapies

19 September 2013

Tissues such as the spinal cord, skeletal muscle and notochord (a structure from which the spine develops in a vertebrate embryo) are formed, at least in part, from a pool of stem cells in the embryo. The maintenance and development of these cells are regulated by several proteins called T-box transcription factors.

Image: Tissues such as the spinal cord, skeletal muscle and notochord are formed, at least in part, from a pool of stem cells in the embryo. The maintenance and development of these cells are regulated by several proteins called T-box transcription factors.

A new study provides important insights into how skeletal muscle and spinal cord tissue are formed in the correct ratio from a pool of stem cells in the frog embryo. 

The work, led by Jim Smith and George Gentsch at the MRC's National Institute for Medical Research (now part of the Francis Crick Institute), will pave the way for the development of stem cell-based treatments for muscle and spinal cord injuries and diseases. 

Dr Gentsch said: "One way to treat injuries and diseases of muscle or spinal cord is to use stem cells to create the appropriate replacement tissue in a way that closely resembles its normal development in our body. Therefore, it is paramount to have a detailed knowledge of how these tissues start to be formed in the embryo." 

The scientists combined several new and classic biological methods to measure and map protein binding to DNA across the whole genome of the frog Xenopus and to assess its function in the embryo. In particular, they studied a family of proteins called T-box transcription factors, which are known to be key to the formation of tissues in the early embryo, but were previously poorly understood. 

"The proximity of protein binding to genes provides helpful clues about which genes are under direct control and vital to the integrity of tissue," explained Dr Gentsch. 

The work was carried out alongside colleagues at the University of Cambridge and the Anne McLaren Laboratory for Regenerative Medicine in Cambridge. 

The team was able to describe how a pool of stem cells in the frog embryo continuously forms tissues such as skeletal muscle and spinal cord at the correct ratio. The work provides evidence for how the T-box family of proteins regulates the growth of these vital tissues during early embryonic development. 

Confirming the findings, embryos lacking T-box proteins failed to develop muscle or other mesodermal cell types, such as connective tissue or bone, and instead formed an excess of neural tissue. 

Dr Gentsch concluded: "The knowledge gained in this study will be important to design effective cell replacement therapies, especially for muscle and spinal cord defects."

The paper, In vivo T-box Transcription Factor Profiling Reveals Joint Regulation of Embryonic Neuro-mesodermal Bipotency, is published in Cell Reports.

  • Research into frog embryos explains how muscle and spinal cord are formed from stem cells, opening up avenues for the development of stem cell-based treatments for muscle and spinal cord injuries and diseases. 
  • Stem cells are immature cells that have not yet developed into the specialised cells that make up our organs and tissues. They can 'self-renew', or make identical copies of themselves, almost indefinitely. They have the potential to be used to treat many human diseases.