title: Anaplastic lymphoma kinase is required for neurogenesis in the developing central nervous system of zebrafish.
abstract: 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.
authors.affiliation: Department of Biological Sciences and Centre for BioImaging Sciences, National University of Singapore, Singapore.
authors.forename: Sheng
authors.initials: S
authors.lastname: Yao
authors.forename: Mangeng
authors.initials: M
authors.lastname: Cheng
authors.forename: Qian
authors.initials: Q
authors.lastname: Zhang
authors.forename: Mariusz
authors.initials: M
authors.lastname: Wasik
authors.forename: Robert
authors.initials: R
authors.lastname: Kelsh
authors.forename: Christoph
authors.initials: C
authors.lastname: Winkler
mesh_terms: D000077548:Anaplastic Lymphoma Kinase; D000818:Animals; D030801:Animals, Genetically Modified; D015153:Blotting, Western; D002454:Cell Differentiation / Q000235:genetics; D049109:Cell Proliferation; D002470:Cell Survival / Q000235:genetics; D002490:Central Nervous System / Q000196:embryology* / Q000201:enzymology; D003001:Cloning, Molecular; D017931:DNA Primers / Q000235:genetics; D017403:In Situ Hybridization; D020287:In Situ Nick-End Labeling; D008845:Microinjections; D060172:Morpholinos; D055495:Neurogenesis / Q000235:genetics / Q000502:physiology*; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics* / Q000378:metabolism*; D017422:Sequence Analysis, DNA; D015027:Zebrafish / Q000196:embryology*
chemical_list: D017931:DNA Primers; D060172:Morpholinos; C000626173:ALK protein, human; D000077548:Anaplastic Lymphoma Kinase; D020794:Receptor Protein-Tyrosine Kinases