Earmuff restricts progenitor cell potential by attenuating the competence to respond to self-renewal factors

Abstract

We also identified that the BAP chromatin-remodeling complex probably functions cooperatively with Erm to restrict the developmental potential of immature INPs. Together, these data led us to conclude that the Erm-BAP-dependent mechanism stably restricts the developmental potential of immature INPs by attenuating their genomic responses to stem cell self-renewal factors. We propose that restriction of developmental potential by the Erm-BAP-dependent mechanism functionally distinguishes intermediate progenitor cells from stem cells, ensuring the generation of differentiated cells and preventing the formation of progenitor cell-derived tumor-initiating stem cells.

Notch maintains Drosophila type II neuroblasts by suppressing the expression of the Fez transcription factor Earmuff

“…However, when Numb is lost or Notch is overactivated, Notch will remain active in imINPs. The active Notch will then continue to suppress Erm in imINPs, which is consistent with a previous report that Erm is never turned on in numb mutant type II NB clones (Janssens et al, 2014). The absence of Erm in imINPs will in turn result in defects in INP maturation and cause subsequent dedifferentiation of INPs into type II NBs, as reported before (Weng et al, 2010).…”

“…Although it remains to be seen if dMyc and Marf are involved in maintaining normal type II NBs, it would be interesting to investigate whether dMyc and mTORC2/AKT signaling have any functional relationship with the suppression of Erm in type II NBs. Our findings concerning the inhibitory role of Notch signaling in PntP1-mediated activation of erm provide insight into why Erm expression is normally restricted in imINPs (Janssens et al, 2014) and why loss of Numb or Notch overactivation leads to overproliferation of type II NBs (Bowman et al, 2008). When type II NBs divide, Numb is asymmetrically segregated into the future imINPs to inhibit Notch activity.…”

“…R9D11-tdTom and R9D11-GFP show similar expression patterns to endogenous Erm proteins, which are detected only in imINPs (except the newly generated imINPs) but not in type II NBs (Fig. 1E,E′,G,I,I′,L,L′,N) (Janssens et al, 2014). Interestingly, when Notch was knocked down or inhibited by Numb, R9D11-tdTom or R9D11-GFP was ectopically expressed in type II NBs (Fig.…”

“…Erm + imINPs are much smaller than NBs and do not express Dpn (Fig. 1L,L′) (Janssens et al, 2014). These data suggest that, in the absence of Notch, Erm is ectopically activated in type II NBs.…”

“…Numb inhibits Notch signaling in immature INPs (imINPs), whereas Brat reduces the activity of Armadillo (Arm; β-catenin) in imINPs (Bowman et al, 2008;Komori et al, 2014b). Erm functions together with the SWI/SNF chromatin-remodeling complex in imINPs to restrict the developmental potential of INPs (Eroglu et al, 2014;Farnsworth et al, 2015;Janssens et al, 2014;Koe et al, 2014). Meanwhile, INPs need to avoid differentiating into GMCs prematurely and exiting the cell cycle.…”