Myhre syndrome (MS) is a condition that presents with a range of developmental problems like
learning difficulties and autism, as well as additional abnormalities such as heart defects, short
stature, and fibrotic complications. It is caused by specific changes in a gene called SMAD4, which makes a
protein that acts as a messenger that communicates signals from outside the cell to the nucleus of
the cell. In respons to these signals, SMAD4 adapts the activity of several genes in the cell.
To understand how the changes in SMAD4 affect brain development, we will study them in different
types of cells, like stem cells and nerve cells. We will evaluate how the mutant SMAD4 protein
interacts with other molecules and DNA in these cells and how this affects gene activity. This will help
us understand what goes wrong in MS during the development of nerve cells.
We will also use zebrafish and mice to see how these changes in SMAD4 affect the development and behavior
of different type of brain cells and what the overall neurological consequences are in this zebrafish
model.
Once we understand what goes wrong in MS, we can test drugs that reverse the abnormal gene
activity which could lead to new treatments.