no child left behind encodes a novel chromatin factor required for germline stem cell maintenance in males but not females

Abstract

SUMMARYMale and female germ cells follow distinct developmental paths with respect to germline stem cell (GSC) production and the types of differentiated progeny they produce (sperm versus egg). An essential aspect of germline development is how sexual identity is used to differentially regulate the male and female germ cell genomes to allow for these distinct outcomes. Here, we identify a gene, no child left behind (nclb), that plays very different roles in the male versus female germline in Drosophila. In particular, nclb is required for GSC maintenance in males, but not in females. Male GSCs mutant for nclb are rapidly lost from the niche, and begin to differentiate but cannot complete spermatogenesis. We further find that nclb encodes a member of a new family of conserved chromatin-associated proteins. NCLB interacts with chromatin in a specific manner and is associated with sites of active transcription. Thus, NCLB appears to be a novel chromatin regulator that exhibits very different effects on the male and female germ cell genomes.

Jak-STAT regulation of cyst stem cell development in the Drosophila testis

“…By L1, this reporter is no longer detected in the testis periphery, and expression in the hub and CySCs becomes stronger, with a gradient of decreasing expression observed in cyst cells away from the hub (Supplemental Figure 4C, D). Interestingly, expression of the 10XSTAT92E-GFP reporter is never detected in germ cells that have previously been shown to activate Jak-STAT signaling in all PGCs and later in GSCs using high-level STAT92E expression as an assay (Casper et al, 2011; Dinardo et al, 2011; Leatherman and Dinardo, 2010; Sheng et al, 2009; Wawersik et al, 2005). Despite this, the expression pattern of the 10XSTAT92E-GFP reporter is similar to that of the Socs36E-PZ enhancer trap in late embryonic and early larval testes (Figure 2E–H).…”

“…This correlates both temporally and spatially with restriction of STAT activity to newly established GSCs and CySCs docked at the hub, and the concomitant loss of STAT activity in posterior germ cells and somatic cells ((Sheng et al, 2009); Supplemental Figure 4). Interestingly, germline STAT activation characterized by high-level STAT92E expression (Casper et al, 2011; Dinardo et al, 2011; Leatherman and Dinardo, 2010; Sheng et al, 2009; Wawersik et al, 2005) is not detected with the 10XSTAT92E-GFP reporter we used to reveal STAT activity in SGPs and CySCs. While the rationale for these differences is not clear, restriction of STAT activity to GSCs and CySC adjacent to the hub correlates both temporally and spatially with the re-distribution of E-Cadherin to the GSC-hub interface (Le Bras and Van Doren, 2006; Sheng et al, 2009).…”

Phf7 Controls Male Sex Determination in the Drosophila Germline

“…These data are consistent with the hypothesis that H3K4me2 has a unique role in regulating the male germline genome. Interestingly, we have recently identified another germline chromatin factor, No child left behind (NCLB), that is expressed in germ cells of both sexes but required for GSC function only in males (Casper et al, 2011). Thus, NCLB may cooperate with PHF7 in regulating the male GSC transcriptional program.…”

Transcriptional regulation during Drosophila spermatogenesis

“…Both NURF 24 , 25 and Scny 23 also regulate female GSC function. By contrast, a novel chromatin factor encoded by no child left behind ( nclb ) specifically regulates male, but not female, GSC maintenance 26 . Nclb is enriched at chromatin regions with active transcription.…”