The Brm-HDAC3-Erm repressor complex suppresses dedifferentiation in Drosophila type II neuroblast lineages

Abstract

The control of self-renewal and differentiation of neural stem and progenitor cells is a crucial issue in stem cell and cancer biology. Drosophila type II neuroblast lineages are prone to developing impaired neuroblast homeostasis if the limited self-renewing potential of intermediate neural progenitors (INPs) is unrestrained. Here, we demonstrate that Drosophila SWI/SNF chromatin remodeling Brahma (Brm) complex functions cooperatively with another chromatin remodeling factor, Histone deacetylase 3 (HDAC3) to suppress the formation of ectopic type II neuroblasts. We show that multiple components of the Brm complex and HDAC3 physically associate with Earmuff (Erm), a type II-specific transcription factor that prevents dedifferentiation of INPs into neuroblasts. Consistently, the predicted Erm-binding motif is present in most of known binding loci of Brm. Furthermore, brm and hdac3 genetically interact with erm to prevent type II neuroblast overgrowth. Thus, the Brm-HDAC3-Erm repressor complex suppresses dedifferentiation of INPs back into type II neuroblasts.DOI: http://dx.doi.org/10.7554/eLife.01906.001

Prevention of medulla neuron dedifferentiation by Nerfin-1 requires inhibition of Notch activity

“…It is obvious that mechanisms must exist to prevent the cells from dedifferentiation. Although proteins that function to keep differentiation have been well studied in other cell types (Bello et al, 2006;Betschinger et al, 2006;Eroglu et al, 2014;Koe et al, 2014;Lee et al, 2006;Wang et al, 2007;Weng et al 2010;Zhang et al, 2016), few have been implicated in postmitotic neuronal maintenance. In the central brain, loss of Midlife crisis (Mdlc), a CCCH zinc-finger protein, results in a decrease in Pros, thus derepressing NB genes in neurons (Carney et al, 2013).…”

The Ets protein pointed prevents both premature differentiation and dedifferentiation of Drosophila intermediate neural progenitors

“…INPs must maintain their self-renewal and avoid differentiation while dividing to produce neurons. However, newly generated INPs are immature and are prone to dedifferentiate into NBs if they fail to differentiate into mature INPs (Bowman et al, 2008;Eroglu et al, 2014;Koe et al, 2014). Thus, Drosophila INPs provide an excellent model for studying how INPs avoid dedifferentiation and premature differentiation.…”

“…For example, preventing the dedifferentiation of immature INPs (imINPs) requires the cell fate determinants Brain tumor (Brat) and Numb, the Fez family transcription factor Earmuff (Erm), as well as the SWI/SNF and Histone deacetylase 3 (HDAC3) chromatin remodeling complexes (Bowman et al, 2008;Eroglu et al, 2014;Koe et al, 2014;Weng et al, 2010). The loss of any of these factors could result in imINP dedifferentiation and supernumerary type II NBs.…”

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

“…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.…”