Models for Trim-NHL proteins in stem cell niches. a) In the Drosophila CNS, neuroblasts (NB) divide asymmetrically to produce a smaller committed daughter termed ganglion mother cell (GMC) and a new neuroblast. An apical (A.) protein complex (or Par complex) directs segregation of basal (B.) determinants including Brat. In most lineages the GMC divides once to produce two neurons (N). b) In the lineage of origin for Brat tumors (PAN), the initial basal daughter is a transit amplifying stem cell (TA) able to undergo further division to generate multiple committed GMCs. In the absence of Brat, TA cells fail to differentiate and hyperproliferate. c) A wild type female Drosophila germarium is depicted (Drosophila ovarian stem cells are reviewed in ref. 112). Polarity is dictated by the Germ cell niche, comprised of the basement membrane and terminal filament (T), cap cells (C) and germ cells (G). Germ cell daughters, or cytoblasts (Cy), undergo four rounds of transit amplifying divisions. Cystoblasts remain connected by cytoplasmic bridges (not shown) and brecome progressively smaller. One cytoblast is determined and differentiates to an oocyte (O, dark). The remaining cystoblasts become nurse cells (N), enclosed in follicular epithelial cells to form an egg chamber. Mei-P26 expression increases during cystoblast transit, as indicated. Expression levels of selected proliferation markers (Cyclin E, d-Myc) that correlate with Mei-P26 are shown. In mei-P26 loss of function mutants cystocyte size is undiminished as the cells hyperproliferate. Differentiation to oocyte and nurse cells is disrupted, with formation of cystic egg chambers. Cyclin E and d-Myc are deregulated. d) A model for Trim32 in the neuroepithelium is depicted. Two radial progenitors (NPC a and b) undergoing interkinetic nuclear migration are shown, with apical feet and basal processes. At division Trim32 accumulates near the thinned basal process, to be differentially inherited by an incipient neuron (N). Expression of Trim32, let-7 and c-Myc in the NPC and neural daughter cells are indicated. A color version of this figure is available at www.landesbioscience.com/curie.