Differential roles of Netrin-1 and its receptor DCC in inferior olivary neuron migration

Netrin-1 was previously shown to be required for the tangential migration and survival of neurons that will form the inferior olivary nucleus (ION). Surprisingly, the compared analysis of mutant mice lacking either Netrin-1 or its major receptor DCC reveals striking phenotypic differences besides common features. Although ectopic stops of ION cell bodies occur in the same positions along the migratory stream in both mutants, the ION neurons' number is not affected by the lack of DCC whereas it is reduced in Netrin-1 mutant mice. Thus, cell death results from the absence of Netrin-1 and not from neuron mis-routing, arguing for a role of Netrin-1 as a survival factor in vivo. The secretion of Netrin-1 by the floor plate (FP) is strictly required – whereas DCC is not – to avoid ION axons' repulsion by the FP and allows them to cross it. Leading processes of neurons of other caudal precerebellar nuclei (PCN) cannot cross the FP in either mutant mouse, suggesting differential sensitivity or mechanism of action of Netrin-1 for leading processes of ION and other PCN neurons.