Understanding Dosage Dependence Mechanisms in Down Syndrome

Collaborators: Rob Meijers & Georgios Skiniotis

Background: Cell adhesion molecules and Down syndrome


Cell adhesion molecules provide cells with identity tags that get cells to cluster together and migrate during tissue development. Without this “molecular glue,” tissues are unable to correctly form, which can have serious developmental implications.  Down Syndrome is a genetic condition resulting from a a full or partial extra copy of chromosome 21. The additional genetic information typically leads to altered physical and cognitive development.  Human Down syndrome cell adhesion molecule (DSCAM) is situated on the distal tip of chromosome 21 and its expression is enhanced in Down syndrome patients.  DSCAM has been associated with congenital heart disease, which is the main cause of death for Down syndrome patients.


Project: Uncovering the structural basis of congentital heart disease related to Down Syndrome

The groups of Rob Meijers (EMBL) and Georgios Skiniotis (Stanford) have initiated structural studies to understand how DSCAM acts as a cell adhesion sensor that seems to be dosage dependent. They have previously showed that Drosophila Dscam engages in isoform specific homodimerization – in other words, Dscam can exist in different forms that have unique and specific properties for binding (Meijers et al. 2007). Using electron microscopy (Skiniotis lab) and X-ray crystallography (Meijers lab), as well as cell biology assays, they have identified different cis/trans conformations that allow a cell to sense that it is involved in cell adhesion with other cells that carry DSCAM on their surface. This process may provide basic insight in the neuronal and heart tissue deficiencies observed in Down syndrome patients.


Find out more:

Interested in finding out more about the Down Syndrome and Cell Adhesion Molecules?  Get in touch, we would love to hear from you!



Structural basis of Dscam isoform specificity
Meijers R, Puetmann-Holgado R, Skiniotis G, et al. Structural basis of Dscam isoform specificity. Nature, 2007 (449) 487-91.