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Wnt signaling is a major determinant of neuroblastoma cell lineages

Szemes, Marianna; Greenhough, Alexander; Malik, Karim

Wnt signaling is a major determinant of neuroblastoma cell lineages Thumbnail


Marianna Szemes

Karim Malik


© 2019 Szemes, Greenhough and Malik. The neural crest (NC), which has been referred to as the fourth germ layer, comprises a multipotent cell population which will specify diverse cells and tissues, including craniofacial cartilage and bones, melanocytes, the adrenal medulla and the peripheral nervous system. These cell fates are known to be determined by gene regulatory networks (GRNs) acting at various stages of NC development, such as induction, specification, and migration. Although transcription factor hierarchies and some of their interplay with morphogenetic signaling pathways have been characterized, the full complexity of activities required for regulated development remains uncharted. Deregulation of these pathways may contribute to tumorigenesis, as in the case of neuroblastoma, a frequently lethal embryonic cancer thought to arise from the sympathoadrenal lineage of the NC. In this “Hypothesis and Theory” article, we utilize the next generation sequencing data from neuroblastoma cells and tumors to evaluate the possible influences of Wnt signaling on NC GRNs and on neuroblastoma cell lineages. We propose that Wnt signaling is a major determinant of regulatory networks that underlie mesenchymal/neural crest cell (NCC)-like cell identities through PRRX1 and YAP/TAZ transcription factors. Furthermore, Wnt may also co-operate with Hedgehog signaling in driving proneural differentiation programmes along the adrenergic (ADRN) lineage. Elucidation of Signaling Regulatory Networks can augment and complement GRNs in characterizing cell identities, which may in turn contribute to the design of improved therapeutics tailored to primary and relapsing neuroblastoma.


Szemes, M., Greenhough, A., & Malik, K. (2019). Wnt signaling is a major determinant of neuroblastoma cell lineages. Frontiers in Molecular Neuroscience, 12(90),

Journal Article Type Article
Acceptance Date Mar 21, 2019
Online Publication Date Apr 16, 2019
Publication Date Feb 12, 2019
Deposit Date Mar 27, 2019
Publicly Available Date May 9, 2019
Journal Frontiers in Molecular Neuroscience
Publisher Frontiers Media
Peer Reviewed Peer Reviewed
Volume 12
Issue 90
Public URL
Publisher URL


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