Neuroblastoma (NB) is a childhood tumor that arises from developing sympathetic ganglia
and adrenal medulla. The restriction of NB to sympathoadrenal tissues is explained
by unique traits of sympathetic neuron and chromaffin cell generation involving proliferation
of already differentiated neuroblasts. Activating mutations in the anaplastic lymphoma
kinase (ALK) gene have been identified in both sporadic and familial forms of NB.
Here, we focus on the normal function of Alk signaling in the control of sympathetic
neurogenesis as well as on effects of mutant Alk. Using loss-of-function approaches
in the chick embryo we demonstrate that Alk signaling is essential for sympathetic
neurogenesis. Forced expression of Alk and constitutively-active Alk mutants increase
proliferation of cultured sympathetic neuroblasts. Alk activation by the ligand Midkine
stimulates neuroblast proliferation and results in enlarged sympathetic ganglia in
the chick embryo. These results demonstrate that neuroblast proliferation in sympathetic
ganglia is controlled by Alk signaling and that NB predisposition by activating Alk
mutations may be explained by effects on the extent and timing of neurogenesis.
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Publication history
Received:
May 15,
2013
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Copyright
© 2013 Published by Elsevier Inc.
