Abstract
ABSTRACTThe development of the nervous system relies on the coordinated regulation of stem cell self-renewal and differentiation. The discovery that brain tumours contain a subpopulation of cells with stem/progenitor characteristics that are capable of sustaining tumour growth has emphasized the importance of understanding the cellular dynamics and the molecular pathways regulating neural stem cell behaviour. By focusing on recent work on glioma and medulloblastoma, we review how lineage tracing contributed to dissecting the embryonic origin of brain tumours and how lineage-specific mechanisms that regulate stem cell behaviour in the embryo may be subverted in cancer to achieve uncontrolled proliferation and suppression of differentiation.
Highlights
Neurological cancers are among the most feared malignancies
Our ability to distinguish cell types in the brain allows us to compare the tumourigenic potential of specific neural stem and progenitor populations. Activation of oncogenes, such as KRasG12D, or inactivation of tumour suppressors, such as p53, Rb, PTEN, Arf or Nf1, has been used to directly address the tumourigenic potential of different cells. These works reveal that neural stem cells (NSCs) and progenitor cells are more readily transformed than differentiated cell types, and embryonic radial glia cells (RGCs) are more prone to transformation than postnatal stem cells (Alcantara Llaguno et al, 2009; Jacques et al, 2010; Munoz et al, 2013)
With over 20% of astrocytomas formed in non-proliferative zones, it follows that either GFAP-positive NSCs have migrated to distant sites, or that tumours originate from mature astrocytes (Chow et al, 2011)
Summary
Neurological cancers are among the most feared malignancies. They include medulloblastoma, the most common malignant brain tumour in children, and high-grade glioblastoma, one of the most lethal adult cancers (Table 1) (Louis et al, 2016). The possibility that neurological cancers are ‘locked in’ to a developmental programme and may retain many of the controls that impinge on these cell populations during development opens up new and exciting opportunities for understanding and targeting these cancers Some of these opportunities are already being exploited in the treatment of paediatric neurological malignancies, where the relationship of cancer cells to spatially and temporally distinct embryonic precursors is better understood (Cavalli et al, 2017; Phoenix et al, 2012; Ramaswamy et al, 2016). Cells with stem-like properties have been isolated from a wide range of paediatric tumours, such as glioma, medulloblastoma, primitive
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
