An intrinsic mechanism controls reactivation of neural stem cells by spindle matrix proteins

Song Li, Chwee Tat Koe, Su Ting Tay, Angie Lay Keng Tan, Shenli Zhang, Yingjie Zhang, Patrick Tan, Wing-Kin Sung and Hongyan Wang ()
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Song Li: Duke-NUS Medical School
Chwee Tat Koe: Duke-NUS Medical School
Su Ting Tay: Duke-NUS Medical School
Angie Lay Keng Tan: Duke-NUS Medical School
Shenli Zhang: Duke-NUS Medical School
Yingjie Zhang: Duke-NUS Medical School
Patrick Tan: Duke-NUS Medical School
Wing-Kin Sung: Genome Institute of Singapore
Hongyan Wang: Duke-NUS Medical School

Nature Communications, 2017, vol. 8, issue 1, 1-12

Abstract: Abstract The switch between quiescence and proliferation is central for neurogenesis and its alteration is linked to neurodevelopmental disorders such as microcephaly. However, intrinsic mechanisms that reactivate Drosophila larval neural stem cells (NSCs) to exit from quiescence are not well established. Here we show that the spindle matrix complex containing Chromator (Chro) functions as a key intrinsic regulator of NSC reactivation downstream of extrinsic insulin/insulin-like growth factor signalling. Chro also prevents NSCs from re-entering quiescence at later stages. NSC-specific in vivo profiling has identified many downstream targets of Chro, including a temporal transcription factor Grainy head (Grh) and a neural stem cell quiescence-inducing factor Prospero (Pros). We show that spindle matrix proteins promote the expression of Grh and repress that of Pros in NSCs to govern their reactivation. Our data demonstrate that nuclear Chro critically regulates gene expression in NSCs at the transition from quiescence to proliferation.

Date: 2017
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DOI: 10.1038/s41467-017-00172-9

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