Neuroblastoma (NB) is a paediatric form of cancer derived from the sympathetic nervous system. Recent genome-wide sequencing data suggest that often NB does not have a clear genetic cause, leading the authors to hypothesize that NB results from aberrations of normal development. To test this hypothesis, Anna Philpott's group used a population of anteroventral noradrenergic (AVNA) cells from Xenopus embryos. These cells share several features with mammalian sympathetic neurons, including the expression of noradrenergic-associated genetic markers such as the achaete-scute complex-like 1 (Ascl1) gene, which encodes a transcriptional driver of neurogenesis. By comparing AVNA and NB cells, the authors found that, whereas Ascl1 is only transiently expressed in AVNA cells, it is aberrantly maintained in NB, where it is phosphorylated on multiple serine-proline sites. The authors then show that differentiation of AVNA cells is enhanced by dephosphorylated Ascl1. Moreover, this process is inhibited by experimental manipulations of NB-associated genes, but, interestingly, dephosphorylation of Ascl1 is able to overcome this inhibition. This work demonstrates that Xenopus AVNA cells represent a unique system to study sympathetic nervous system development and its relationship to NB. Moreover, it suggests that Asc11 phosphorylation might promote stalled differentiation leading to NB, thus identifying a potential target for therapeutic purposes. Page
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May 2015
Development/DMM Virtual Meeting 2021
Welcoming new Editors to DMM
Editor-in-Chief Liz Patton wants DMM to strengthen its presence in the field of translational biology and to focus on the importance of disease mechanisms, just as much as models. To implement this vision, we are pleased to welcome new Editors Sally Dunwoodie (Victor Chang Cardiac Research Institute, Australia), Monkol Lek (Yale School of Medicine, USA) and Rickie Patani (Francis Crick Institute, London, UK) to the team.
Roles of the gut microbiome in colorectal cancer development
Going hand-in-hand, a new Perspective by Foegeding et al. explores the Western diet as a driver of dysbiosis in colorectal cancer while a new Review by Wang et al. focuses on microbiota-driven mechanisms that initiate sporadic colorectal cancer.
preLights – the latest disease modelling preprints
Head over to preLights for the digests of the latest preprints:
Erin McGregor highlights work by Nowicka et al. that suggests a potential connection between mitochondrial dysfunction and neurodegeneration.
Emma Wilson discusses work by Dagra et al., which highlights D2 receptors as a potential target that could be used to alleviate alpha-Synuclein pathology in Parkinson’s disease.
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