TY - JOUR
T1 - Dissecting Hes-centred transcriptional networks in neural stem cell maintenance and tumorigenesis in Drosophila
AU - Magadi, Srivathsa S.
AU - Voutyraki, Chrysanthi
AU - Anagnostopoulos, Gerasimos
AU - Zacharioudaki, Evanthia
AU - Poutakidou, Ioanna K.
AU - Efraimoglou, Christina
AU - Stapountzi, Margarita
AU - Theodorou, Vasiliki
AU - Nikolaou, Christoforos
AU - Koumbanakis, Konstantinos A.
AU - Fullard, John F.
AU - Delidakis, Christos
N1 - Publisher Copyright:
© 2020. Published by The Company of Biologists Ltd
PY - 2020/11/1
Y1 - 2020/11/1
N2 - Neural stem cells divide during embryogenesis and juvenile life to generate the entire complement of neurons and glia in the nervous system of vertebrates and invertebrates. Studies of the mechanisms controlling the fine balance between neural stem cells and more differentiated progenitors have shown that, in every asymmetric cell division, progenitors send a Delta-Notch signal to their sibling stem cells. Here, we show that excessive activation of Notch or overexpression of its direct targets of the Hes family causes stem-cell hyperplasias in the Drosophila larval central nervous system, which can progress to malignant tumours after allografting to adult hosts. We combined transcriptomic data from these hyperplasias with chromatin occupancy data for Dpn, a Hes transcription factor, to identify genes regulated by Hes factors in this process. We show that the Notch/Hes axis represses a cohort of transcription factor genes. These are excluded from the stem cells and promote early differentiation steps, most likely by preventing the reversion of immature progenitors to a stem-cell fate. We describe the impact of two of these 'anti-stemness' factors, Zfh1 and Gcm, on Notch/Hes-triggered tumorigenesis.
AB - Neural stem cells divide during embryogenesis and juvenile life to generate the entire complement of neurons and glia in the nervous system of vertebrates and invertebrates. Studies of the mechanisms controlling the fine balance between neural stem cells and more differentiated progenitors have shown that, in every asymmetric cell division, progenitors send a Delta-Notch signal to their sibling stem cells. Here, we show that excessive activation of Notch or overexpression of its direct targets of the Hes family causes stem-cell hyperplasias in the Drosophila larval central nervous system, which can progress to malignant tumours after allografting to adult hosts. We combined transcriptomic data from these hyperplasias with chromatin occupancy data for Dpn, a Hes transcription factor, to identify genes regulated by Hes factors in this process. We show that the Notch/Hes axis represses a cohort of transcription factor genes. These are excluded from the stem cells and promote early differentiation steps, most likely by preventing the reversion of immature progenitors to a stem-cell fate. We describe the impact of two of these 'anti-stemness' factors, Zfh1 and Gcm, on Notch/Hes-triggered tumorigenesis.
KW - Cancer models in Drosophila
KW - Drosophila
KW - Hes
KW - Neural stem cells
KW - Notch signalling
KW - Transcription factors
UR - http://www.scopus.com/inward/record.url?scp=85096738560&partnerID=8YFLogxK
U2 - 10.1242/dev.191544
DO - 10.1242/dev.191544
M3 - Article
C2 - 33229432
AN - SCOPUS:85096738560
SN - 0950-1991
VL - 147
JO - Development (Cambridge)
JF - Development (Cambridge)
IS - 22
M1 - dev191544
ER -