Temporal patterning in neural progenitors: from Drosophila development to childhood cancers.

Cédric Maurange

doi:10.1242/dmm.044883

Abstract

ABSTRACTThe developing central nervous system (CNS) is particularly prone to malignant transformation, but the underlying mechanisms remain unresolved. However, periods of tumor susceptibility appear to correlate with windows of increased proliferation, which are often observed during embryonic and fetal stages and reflect stereotypical changes in the proliferative properties of neural progenitors. The temporal mechanisms underlying these proliferation patterns are still unclear in mammals. In Drosophila, two decades of work have revealed a network of sequentially expressed transcription factors and RNA-binding proteins that compose a neural progenitor-intrinsic temporal patterning system. Temporal patterning controls both the identity of the post-mitotic progeny of neural progenitors, according to the order in which they arose, and the proliferative properties of neural progenitors along development. In addition, in Drosophila, temporal patterning delineates early windows of cancer susceptibility and is aberrantly regulated in developmental tumors to govern cellular hierarchy as well as the metabolic and proliferative heterogeneity of tumor cells. Whereas recent studies have shown that similar genetic programs unfold during both fetal development and pediatric brain tumors, I discuss, in this Review, how the concept of temporal patterning that was pioneered in Drosophila could help to understand the mechanisms of initiation and progression of CNS tumors in children.

Highlights

Introduction: the developmental origins of central nervous system (CNS) tumors in children It is well accepted that the etiology of adult and childhood cancers underlies different mechanisms and principles
The different types of medulloblastoma, the most frequent CNS tumors in children, appear to all originate from different fetal precursors of the cerebellum and dorsal brain stem (Gibson et al, 2010; Vladoiu et al, 2019), while fetal glialcommitted progenitors could be at the root of pediatric high-grade gliomas (Jessa et al, 2019; Pathania et al, 2017)
Work on human retinal progenitors has demonstrated that retinoblastomas originate from cone photoreceptor precursors produced during fetal development (Xu et al, 2014), whereas cells of the early neural crest, an embryonic structure lying on the dorsal side of the neural tube, may be the cells of origin of some atypical teratoid rhabdoid tumors (ATRTs) (Vitte et al, 2017)

Summary

Introduction

Introduction: the developmental origins of CNS tumors in children It is well accepted that the etiology of adult and childhood cancers underlies different mechanisms and principles. Temporal patterning is the mechanism by which stem cells or progenitors change their competence as development progresses in order to generate different types of differentiated progeny.

Results

Conclusion