The Dcc gene was discovered as investigators searched for causes of colorectal carcinoma [33]. This gene is deleted in approximately 70% of colorectal carcinomas leading to the hypothesis that Dcc is a tumor suppressor gene [28, 34]. At the same time a seemingly very separate type of function has been demonstrated for DCC protein, that of an axonal guidance molecule serving as a receptor for netrin-1 [26, 27]. In addition to misrouting of axons caused by DCC deficiency, reduced levels of this protein alter patterns of synaptic connections within the developing CNS as well as synaptic plasticity within the adult brain [21, 23, 35]. The integrity of DCC-mediated netrin-1 signaling is required in the development of multiple central and peripheral nervous system structures including the prefrontal cortex, visual system and spinal cord [23, 36–38]. Major structural and organizational changes such as failure of axons to cross the midline have been attributed to DCC signaling insufficiency, even when loss of Dcc expression and function are only partial [21, 24, 39]. The Dcc gene itself codes for a single transmembrane spanning receptor
