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Wnt Signaling Is a Major Determinant of Neuroblastoma Cell Lineages

Research output: Contribution to journalArticle

Original languageEnglish
Article number90
Number of pages14
JournalFrontiers in Molecular Neuroscience
Volume12
DOIs
DateAccepted/In press - 21 Mar 2019
DatePublished (current) - 16 Apr 2019

Abstract

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.

    Research areas

  • wnt signaling, neuroblastoma, neural crest, gene regulatory networkd, Hippo YAP/TAZ, Hedgehog signalling

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    Rights statement: This is the final published version of the article (version of record). It first appeared online via Frontiers at https://www.frontiersin.org/articles/10.3389/fnmol.2019.00090/full. Please refer to any applicable terms of use of the publisher.

    Final published version, 4 MB, PDF-document

    Licence: CC BY

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