FUNCTIONAL ANALYSIS OF ANAPLASTIC LYMPHOMA KINASE DURING EMBRYONIC NEUROGENESIS IN ZEBRAFISH
The orphan receptor tyrosine kinase gene Anaplastic Lymphoma Kinase (ALK) was initially discovered as an oncogene. ALK kinase over-activation has been associated with human cancers, most importantly neuroblastoma. However, little is known about ALK¿s endogenous function in development. I identified an alk ortholog in zebrafish and used this model species to analyze the embryonic function of alk. Zebrafish alk is highly expressed in the central nervous system (CNS) during embryonic development. Constitutive overexpression of non-mutated alk in a heat shock inducible transgenic zebrafish line resulted in ectopic MAPK activation, elevated cell proliferation, disruption of neurogenesis patterns, as well as mis-positioning of differentiated neurons. Loss-of-function in alk by, Morpholino knock-down and a small molecule inhibitor compromised neuronal differentiation and neuron survival in the CNS, but left progenitor formation intact. Also Midkine, a putative ligand for Alk and receptor protein tyrosine phosphatase zeta (RPTPz), a known Alk interactor, are briefly discussed.
anaplastic lymphoma kinase, midkine, neurogenesis, proliferation, apoptosis, zebrafish
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