Skip to main page content (V体育2025版)
U.S. flag

An official website of the United States government

Dot gov

The . gov means it’s official. Federal government websites often end in . gov or . mil. Before sharing sensitive information, make sure you’re on a federal government site VSports app下载. .

Https

The site is secure. The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely V体育官网. .

. 2011 Nov;138(21):4699-708.
doi: 10.1242/dev.072157.

"V体育ios版" Midkine and Alk signaling in sympathetic neuron proliferation and neuroblastoma predisposition

Tobias Reiff  1 , Leslie Huber, Marco Kramer, Olivier Delattre, Isabelle Janoueix-Lerosey, Hermann Rohrer
Affiliations

V体育官网入口 - Midkine and Alk signaling in sympathetic neuron proliferation and neuroblastoma predisposition

Tobias Reiff et al. Development. 2011 Nov.

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 VSports手机版. .

PubMed Disclaimer

"V体育安卓版" Publication types

MeSH terms

"V体育ios版" LinkOut - more resources