A balancing act in the inner ear

The generation of complex three-dimensional structures is one of the most remarkable feats of embryonic development, but in many cases little is known about how such structures are achieved. Now, Lisa Goodrich and colleagues report that the formation of the mouse inner ear, which houses the sensory organs for hearing and balance, requires a previously unrecognised feedback loop between the morphogen netrin 1 (Ntn1) and the immunoglobulin superfamily protein Lrig3 (see p. 4091). During a mutagenesis screen, the authors found that the lateral canal (a component of the inner ear) of Lrig3 mutant mice is truncated. This, they report, is due to the accelerated fusion of the opposing walls of a precursor structure known as the lateral pouch, which is caused by ectopically expressed Ntn1 triggering basement membrane breakdown. The authors demonstrate further that cross-repressive interactions between Lrig3 and Ntn1 define the fusing and non-fusing domains of the lateral pouch during lateral canal morphogenesis, and propose that this interaction constitutes a novel mechanism for Ntn1 regulation.