|
Work
with zebrafish embryos identifies protein interaction and timing of the key
regulator
Caption: Graphic depicts protein interaction in muscle formation: The
bottom embryo is normal, not yet expressing the early muscle genes. In the top
embryo, researchers forced early expression of Smarcd3, which switches on the
muscle genes (dark blue) earlier than normal. This and other experiments showed
that Smarcd3 is the limiting factor that regulates when a cell will turn into a
muscle. The middle part shows the Smarcd3-protein complex (pink, orange, green)
altering the shape of the chromosome
|
University
of Oregon scientists say they have identified a gene that is the key switch that
allows embryonic cells to form into muscles in zebrafish.
Much
like students in a kindergarten class lining up to go to lunch, the trigger
gene, which is identified as Smarcd3, must align correctly with two other genes
for muscle formation to begin, a process known as myogenesis, said principal
investigator Monte Westerfield, a professor of biology and researcher in the UO
Institute of Neuroscience.
The
basic research, funded by the National Institutes of Health, was done using
zebrafish embryos, which provide a model system for analyzing the genetic
control of induction and specification of muscle cells in vertebrates, as well
as for many other important health issues. The findings were published online
ahead of the regular publication by the Journal of Biological
Chemistry.
"Our
muscles develop from a particular set of cells in the embryo," Westerfield said.
"These muscle precursor cells need to be in the right place at the right time to
develop into muscles. Previously it was unknown how the timing of this critical
developmental switch is controlled. We discovered the missing factor, Smarcd3,
which forms a protein complex that alters the shape of DNA in particular regions
of the genome, thus turning on genes required for cells to develop into
muscle."
Smarcd3
proteins are part of a chromatin-remodeling complex made up of DNA and proteins
that Make Up chromosomes. It is a transcriptional protein, which means it is
important for initiating, in this case, development.
The UO
researchers found that muscle formation begins in an embryo's mesoderm when
Smarcd3 interacts correctly with two other transcription-factors known as Fgf
and Ntl. This specific time-sensitive alignment, the researchers noted, works to
trigger the earliest gene expression involved in
myogenesis.
Previous
research had suggested the requirement of several additional transcription
proteins, but the UO team was able to sort through many of the combinations and
narrow the field to these three factors. The findings could eventually allow
researchers to understand how various combinations of proteins in the chromatin
act to regulate the development of different cell types, tissues and
organs.
###
Co-authors
with Westerfield of the JBC paper were two former research associates in
Westerfield's lab: Haruki Ochia, who recently left the UO for the Nara Institute
of Science and Technology in Japan, and Stefan Hans, who now is at the
University of Technology in Dresden, Germany.
|
Research and Review 
