DSCAM promotes self-avoidance in the developing mouse retina by masking the functions of cadherin superfamily members

Significance Cell adhesion molecules (CAMs) provide highly specific cell-surface recognition signals by which developing neurons interact with specific partners. However, these CAMs are common between neurons of the same type, and without a mechanism of self-avoidance or of homotypic avoidance, developing neurons will excessively adhere with themselves. This self-avoidance can be promoted by extreme molecular diversity, such as that ofDscam1 (Down syndrome cell adhesion molecule 1) in flies, which gives neurons distinct barcodes. MouseDscam, on the other hand, promotes self-avoidance without molecular diversity. Here, we provide evidence that DSCAM can functionally interact with other CAMs, called cadherins and protocadherins, to act like a general “nonstick” signal. Through this “adhesive masking” mechanism, DSCAM allows neurons to develop their appropriate shapes, positions, and connections.