Childhood neuroblastoma, a neuroendocrine tumour of the peripheral sympathetic nervous system, is associated with amplification of the MYCN oncogene and mutational activation of ALK (encoding anaplastic lymphoma kinase). Models that clarify whether and how these genes interact in the development of neuroblastoma are limited. Zhu et al. generated transgenic zebrafish overexpressing human MYCN and activated ALK, resulting in tumours that closely mimic those observed in the human disease. The authors show that MYCN over-expression alone causes aberrant neuroblast hyperplasia early during development, which is offset in part by a subsequent apoptotic event; surviving MYCN-over-expressing cells fail to differentiate and give rise to neuroblastoma. Co-expression of mutationally activated ALK blocks the apoptotic event but does not restore neuroblast differentiation, tripling penetrance and accelerating the onset of neuroblastoma. These results provide insight into the synergistic relationship between two important mediators of neuroblastoma, and could help in developing treatments for the disease.
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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