'Nonstick' molecule enables correct neural development

JAX Professor, Rob Burgess,, neuroscience

DSCAM interacts with other cell adhesion molecules to prevent their running amok.

Developing neurons need to connect with specific partners. Cell adhesion molecules (CAMs) make a kind of “cell” call, sending connecting signals between neurons. But how do neurons of the same type avoid making too many connections, resulting in excessive clumping?

One of nature’s strategies is extreme molecular diversity, like giving each neuron a unique cell phone number or bar code. This occurs in insects thanks to Dscam1 (Down syndrome cell adhesion molecule 1).

A Jackson Laboratory (JAX) research team found a related but different mechanism in mice. “Mouse Dscam promotes self-avoidance without molecular diversity,” says Rob Burgess, Ph.D.Studies the molecular mechanisms of synapse formation, development and maintenance in peripheral neuromuscular junctions and retina.JAX Professor Rob Burgess, Ph.D. , senior author of a paper in the Proceedings of the National Academy of Sciences. “We show that DSCAM can functionally interact with other CAMs, called cadherins and protocadherins, and acts like a general ‘nonstick’ signal. Through this ‘adhesive masking’ mechanism, DSCAM allows neurons to develop their appropriate shapes, positions and connections.”

The researchers focused on DSCAM’s self-avoidance function in the mouse retina, but DSCAM and members of the cadherin superfamily have also emerged as key contributors to a variety of neurodevelopmental disorders, including autism, schizophrenia, bipolar disease, Down syndrome and intellectual disability. “Indeed, de novo mutations in DSCAM have been linked to autism spectrum disorder in three families,” Burgess notes.

The team plans further investigation of the cell types in which DSCAM functions and the molecular mechanisms by which DSCAM masks adhesion, to advance understanding of normal development as well as the potential mechanisms underlying neurodevelopmental disorders.

Garrett et al.: DSCAM promotes self-avoidance in the developing mouse retina by masking the functions of cadherin superfamily members. Proceedings of the National Academy of Sciences, Oct. 8, 2018, www.pnas.org/cgi/doi/10.1073/pnas.1809430115