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Anaplastic Lymphoma Kinase  ( ALK ) was initially discovered as an oncogene in human lymphoma and other cancers, including neuroblastoma. However, little is known about the physiological function of ALK. We identified the  alk  ortholog in zebrafish ( Danio rerio ) and found that it is highly expressed in the developing central nervous system (CNS). Heat-shock inducible transgenic zebrafish lines were generated to over-express  alk  during early neurogenesis. Its ectopic expression resulted in activation of the MEK/ERK pathway, increased cell proliferation, and aberrant neurogenesis leading to mis-positioning of differentiated neurons. Thus, overexpressed  alk  is capable of promoting cell proliferation in the nervous system, similar to the situation in  ALK -related cancers. Next, we used Morpholino mediated gene knock-down and a pharmacological inhibitor to interfere with expression and function of endogenous Alk. Alk inhibition did not affect neuron progenitor formation but severely compromised neuronal differentiation and neuron survival in the CNS. These data indicate that tightly controlled  alk  expression is critical for the balance between neural progenitor proliferation, differentiation and survival during embryonic neurogenesis.

Anaplastic Lymphoma Kinase Is Required for Neurogenesis in the Developing Central Nervous System of Zebrafish