English
 
User Manual Privacy Policy Disclaimer Contact us
  Advanced SearchBrowse

Item

ITEM ACTIONSEXPORT
 
 
DownloadE-Mail
  Midkine and Alk signaling in sympathetic neuron proliferation and neuroblastoma predisposition

Reiff, T., Huber, L., Kramer, M., Delattre, O., Janoueix-Lerosey, I., & Rohrer, H. (2011). Midkine and Alk signaling in sympathetic neuron proliferation and neuroblastoma predisposition. Development, 138(21), 4699-4708.

Item is

Basic

show hide
Item Permalink: http://hdl.handle.net/11858/00-001M-0000-002E-1D0B-6 Version Permalink: http://hdl.handle.net/11858/00-001M-0000-002E-1D0C-4
Genre: Journal Article

Files

show Files

Locators

show

Creators

show
hide
 Creators:
Reiff, T.1, Author              
Huber, L.1, Author              
Kramer, M.2, Author              
Delattre, O., Author
Janoueix-Lerosey, I., Author
Rohrer, H.2, Author              
Affiliations:
1Neurochemistry Department, Max Planck Institute for Brain Research, Max Planck Society, ou_2461704              
2Developmental Neurobiology Group, Max Planck Institute for Brain Research, Max Planck Society, ou_2461697              

Content

show
hide
Free keywords: -
 Abstract: Neuroblastoma (NB) is the most common extracranial solid tumor in childhood and arises from cells of the developing sympathoadrenergic lineage. Activating mutations in the gene encoding the ALK tyrosine kinase receptor predispose for NB. Here, we focus on the normal function of Alk signaling in the control of sympathetic neuron proliferation, as well as on the effects of mutant ALK. Forced expression of wild-type ALK and NB-related constitutively active ALK mutants in cultures of proliferating immature sympathetic neurons results in a strong proliferation increase, whereas Alk knockdown and pharmacological inhibition of Alk activity decrease proliferation. Alk activation upregulates NMyc and trkB and maintains Alk expression by an autoregulatory mechanism involving Hand2. The Alk-ligand Midkine (Mk) is expressed in immature sympathetic neurons and in vivo inhibition of Alk signaling by virus-mediated shRNA knockdown of Alk and Mk leads to strongly reduced sympathetic neuron proliferation. Taken together, these results demonstrate that the extent and timing of sympathetic neurogenesis is controlled by Mk/Alk signaling. The predisposition for NB caused by activating ALK mutations may thus be explained by aberrations of normal neurogenesis, i.e. elevated and sustained Alk signaling and increased NMyc expression.

Details

show
hide
Language(s): eng - English
 Dates: 2011
 Publication Status: Published in print
 Pages: -
 Publishing info: -
 Table of Contents: -
 Rev. Type: -
 Identifiers: eDoc: 579111
ISI: 000296060100013
 Degree: -

Event

show

Legal Case

show

Project information

show

Source 1

show
hide
Title: Development
Source Genre: Journal
 Creator(s):
Affiliations:
Publ. Info: -
Pages: - Volume / Issue: 138 (21) Sequence Number: - Start / End Page: 4699 - 4708 Identifier: ISSN: 0950-1991