Molekulare und genetische Medizin

Neuroblastoma Associated Genes Are Enriched in Trunk Neural Crest

Abstract

Persson CU and Mohlin S

Neural crest is a remarkable transient cell population present during embryogenesis, with the ability to differentiate into a multitude of cell types. Depending on anterior to posterior position, neural crest derivatives (cranial, vagal, trunk and sacral, respectively) migrate and commit to restricted lineages. Neuroblastoma is a tumor of infancy and locates along sympathetic ganglia. Based on tumor location and tumor cell gene expression, neuroblastoma is believed to arise from cells of the trunk neural crest-derived sympathetic nervous system. Here we establish the gene expression pattern of trunk enriched- as well as neuroblastoma associated genes over time during early embryogenesis. We show that genes associated with trunk neural crest development as well as neuroblastoma progression are highly expressed at time points when trunk neural crest cells delaminate from the neural tube, undergo epithelial-to-mesenchymal transition and migrate throughout the embryonic body. Using recently established crestosphere cultures – in vitro maintenance of multipotent and self-renewing neural crest stem cells – we confirm that diagnostic and prognostic markers of neuroblastoma are highly enriched in trunk- as compared to cranial neural crest. Our data strengthen a trunk neural crest origin for neuroblastoma