Anaplastic Lymphoma Kinase is required for neurogenesis in the developing central nervous system of zebrafish

S. Yao, M. Cheng, Q. Zhang, M. Wasik, R. Kelsh, C. Winkler

Research output: Contribution to journalArticle

27 Citations (Scopus)
78 Downloads (Pure)

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.
Original languageEnglish
Article numbere63757
JournalPLoS ONE
Volume8
Issue number5
DOIs
Publication statusPublished - 10 May 2013

Fingerprint

neurogenesis
Neurogenesis
Neurology
Zebrafish
lymphoma
Danio rerio
Neurons
central nervous system
phosphotransferases (kinases)
Central Nervous System
Cell proliferation
neurons
Cell Proliferation
Gene Knockdown Techniques
Morpholinos
cell proliferation
MAP Kinase Signaling System
Mitogen-Activated Protein Kinase Kinases
Neuroblastoma
Oncogenes

Cite this

Anaplastic Lymphoma Kinase is required for neurogenesis in the developing central nervous system of zebrafish. / Yao, S.; Cheng, M.; Zhang, Q.; Wasik, M.; Kelsh, R.; Winkler, C.

In: PLoS ONE, Vol. 8, No. 5, e63757, 10.05.2013.

Research output: Contribution to journalArticle

Yao, S. ; Cheng, M. ; Zhang, Q. ; Wasik, M. ; Kelsh, R. ; Winkler, C. / Anaplastic Lymphoma Kinase is required for neurogenesis in the developing central nervous system of zebrafish. In: PLoS ONE. 2013 ; Vol. 8, No. 5.
@article{b6fa699d7f9f4caaa19875f14a58486e,
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.",
author = "S. Yao and M. Cheng and Q. Zhang and M. Wasik and R. Kelsh and C. Winkler",
year = "2013",
month = "5",
day = "10",
doi = "10.1371/journal.pone.0063757",
language = "English",
volume = "8",
journal = "PLoS ONE",
issn = "1932-6203",
publisher = "Public Library of Science (PLOS)",
number = "5",

}

TY - JOUR

T1 - Anaplastic Lymphoma Kinase is required for neurogenesis in the developing central nervous system of zebrafish

AU - Yao, S.

AU - Cheng, M.

AU - Zhang, Q.

AU - Wasik, M.

AU - Kelsh, R.

AU - Winkler, C.

PY - 2013/5/10

Y1 - 2013/5/10

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=84877302754&partnerID=8YFLogxK

UR - http://dx.doi.org/10.1371/journal.pone.0063757

U2 - 10.1371/journal.pone.0063757

DO - 10.1371/journal.pone.0063757

M3 - Article

VL - 8

JO - PLoS ONE

JF - PLoS ONE

SN - 1932-6203

IS - 5

M1 - e63757

ER -