Universität zu Köln

Voutyraki, Chrysanthi, Choromidis, Alexandros, Theodorou, Vasiliki ORCID: 0000-0003-1614-700X, Efraimoglou, Christina, Anagnostopoulos, Gerasimos, Magadi, Srivathsa S., Grammenoudi, Sofia, Zacharioudaki, Evanthia ORCID: 0000-0002-1641-9645 and Delidakis, Christos (2022). Repression of differentiation genes by Hes transcription factors fuels neural tumour growth in Drosophila. Int. J. Dev. Biol., 66 (1-3). S. 211 - 223. BILBAO: UNIV BASQUE COUNTRY UPV-EHU PRESS. ISSN 1696-3547

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Abstract

Background: Neural stem cells (NSC) in divide asymmetrically to generate one cell that retains stem cell identity and another that is routed to differentiation. Prolonged mitotic activity of the NSCs gives rise to the plethora of neurons and glial cells that wire the brain and nerve cord. Genetic insults, such as excess of Notch signaling, perturb the normal NSC proliferation programs and trigger the formation of NSC hyperplasias, which can subsequently progress to malignancies. Hes proteins are crucial mediators of Notch signaling, and in the NSC context they act by repressing a cohort of early pro-differentiation transcription factors. Downregulation of these pro-differentiation factors makes NSC progeny cells susceptible to adopting an aberrant stem cell program. We have recently shown that Hes overexpression in Drosophila leads to NSC hyperplasias that progress to malignant tumours after allografting to adult hosts. Methods: We have combined genetic analysis, tissue allografting and transcriptomic approaches to address the role of Hes genes in NSC malignant transformation. Results: We show that the E (spl) genes are important mediators in the progression of Notch hyperplasias to malignancy, since allografts lacking the E (spl) genes grow much more slowly. We further present RNA profiling of Hes-induced tumours at two different stages after allografting. We find that the same cohort of differentiation-promoting transcription factors that are repressed in the primary hyperplasias continue to be downregulated after transplantation. This is accompanied by an upregulation of stress-response genes and metabolic reprogramming. Conclusions: The combination of dedifferentiation and cell physiology changes most likely drive tumour growth.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Voutyraki, Chrysanthi UNSPECIFIED UNSPECIFIED UNSPECIFIED Choromidis, Alexandros UNSPECIFIED UNSPECIFIED UNSPECIFIED Theodorou, Vasiliki UNSPECIFIED orcid.org/0000-0003-1614-700X UNSPECIFIED Efraimoglou, Christina UNSPECIFIED UNSPECIFIED UNSPECIFIED Anagnostopoulos, Gerasimos UNSPECIFIED UNSPECIFIED UNSPECIFIED Magadi, Srivathsa S. UNSPECIFIED UNSPECIFIED UNSPECIFIED Grammenoudi, Sofia UNSPECIFIED UNSPECIFIED UNSPECIFIED Zacharioudaki, Evanthia UNSPECIFIED orcid.org/0000-0002-1641-9645 UNSPECIFIED Delidakis, Christos UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-692473
DOI:	10.1387/ijdb.210187cd
Journal or Publication Title:	Int. J. Dev. Biol.
Volume:	66
Number:	1-3
Page Range:	S. 211 - 223
Date:	2022
Publisher:	UNIV BASQUE COUNTRY UPV-EHU PRESS
Place of Publication:	BILBAO
ISSN:	1696-3547
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language REGULATES SELF-RENEWAL; ASYMMETRIC SEGREGATION; STEM-CELLS; NEXT-GENERATION; SUPPRESSOR; PROSPERO; PROTEIN; NOTCH; BRAT; PROLIFERATION Multiple languages Developmental Biology Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/69247