Neuroblastoma, the most common extracranial solid tumour in childhood, arises from cells of the developing sympathoadrenergic lineage. Activating mutations in the gene encoding the tyrosine kinase receptor anaplastic lymphoma kinase (ALK) have been identified in both familial and sporadic cases of neuroblastoma so might Alk signalling control proliferation in this lineage? On , Hermann Rohrer and colleagues report that forced expression of wild-type ALK or neuroblastoma-related constitutively active mutant ALK increases the proliferation of cultured immature chick sympathetic neurons and their expression of the proto-oncogene NMyc and of the neurotrophin receptor trkB. By contrast, Alk knockdown both in vitro and in vivo reduces sympathetic neuron proliferation. Furthermore, the Alk ligand Midkine (Mk) is expressed in immature sympathetic neurons, they report, and in vivo knockdown of Mk also reduces sympathetic neuron proliferation. Together, these results indicate that Mk/Alk signalling controls the extent and timing of sympathetic neurogenesis. Thus, the predisposition to neuroblastoma that is associated with activating ALK mutations might be the result of aberrant neurogenesis.
