Although much is known about the specification and differentiation of midbrain dopaminergic (mDA) neurons, the mechanisms regulating their migration within the ventral midbrain (VM) are poorly understood. Migration of several other neuronal types is under the control of CXCL12/CXCR4 signalling, which has been shown to impact on migration, neuritogenesis and axonal pathfinding. Now, Ernest Arenas and colleagues () set out to investigate whether this chemokine pathway might also regulate mDA neuron migration. They find that Cxcl12 is expressed in the meninges surrounding the VM, whereas the Cxcr4 receptor is expressed in the mDA neurons and their precursors. Using both in vitro culture and in vivo approaches, the authors show that mDA neurons migrate towards the meningeal source of CXCL12, in a Cxcr4-dependent manner; importantly, in Cxcr4 mutant embryos, mDA neurons are misplaced. Moreover, neuritogenesis of these neurons is impaired when CXCL12/CXCR4 signalling is perturbed. Together, these results reveal a key role for this chemokine pathway in the regulation of mDA neuron migration.
