Neural stem cell quiescence and stemness are molecularly distinct outputs of the notch3 signalling cascade in the vertebrate adult brain

TY - JOUR

T1 - Neural stem cell quiescence and stemness are molecularly distinct outputs of the notch3 signalling cascade in the vertebrate adult brain

AU - Than-Trong, Emmanuel

AU - Ortica-Gatti, Sara

AU - Mella, Sébastien

AU - Nepal, Chirag

AU - Alunni, Alessandro

AU - Bally-Cuif, Laure

PY - 2018

Y1 - 2018

N2 - Neural stem cells (NSCs) in the adult vertebrate brain are found in a quiescent state and can preserve long-lasting progenitor potential (stemness). Whether and how these two properties are linked, and to what extent they can be independently controlled by NSC maintenance pathways, is unresolved. We have previously identified Notch3 signalling as a major quiescence-promoting pathway in adult NSCs of the zebrafish pallium. We now show that Notch3 also controls NSC stemness. Using parallel transcriptomic characterizations of notch3 mutant NSCs and adult NSC physiological states, we demonstrate that a set of potentially direct Notch3 target genes distinguishes quiescence and stemness control. As a proof of principle, we focus on one ‘stemness’ target, encoding the bHLH transcription factor Hey1, that has not yet been analysed in adult NSCs. We show that abrogation of Hey1 function in adult pallial NSCs in vivo, including quiescent NSCs, leads to their differentiation without affecting their proliferation state. These results demonstrate that quiescence and stemness are molecularly distinct outputs of Notch3 signalling, and identify Hey1 as a major Notch3 effector controlling NSC stemness in the vertebrate adult brain.

AB - Neural stem cells (NSCs) in the adult vertebrate brain are found in a quiescent state and can preserve long-lasting progenitor potential (stemness). Whether and how these two properties are linked, and to what extent they can be independently controlled by NSC maintenance pathways, is unresolved. We have previously identified Notch3 signalling as a major quiescence-promoting pathway in adult NSCs of the zebrafish pallium. We now show that Notch3 also controls NSC stemness. Using parallel transcriptomic characterizations of notch3 mutant NSCs and adult NSC physiological states, we demonstrate that a set of potentially direct Notch3 target genes distinguishes quiescence and stemness control. As a proof of principle, we focus on one ‘stemness’ target, encoding the bHLH transcription factor Hey1, that has not yet been analysed in adult NSCs. We show that abrogation of Hey1 function in adult pallial NSCs in vivo, including quiescent NSCs, leads to their differentiation without affecting their proliferation state. These results demonstrate that quiescence and stemness are molecularly distinct outputs of Notch3 signalling, and identify Hey1 as a major Notch3 effector controlling NSC stemness in the vertebrate adult brain.

KW - Hey1

KW - Neural stem cell

KW - Notch3

KW - Pallium

KW - Quiescence

KW - Stemness

U2 - 10.1242/dev.161034

DO - 10.1242/dev.161034

M3 - Journal article

C2 - 29695612

AN - SCOPUS:85047974848

SN - 0950-1991

VL - 145

SP - 1

EP - 14

JO - Development (Cambridge)

JF - Development (Cambridge)

IS - 10

M1 - dev161034

ER -