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.