scholarly journals The Bric-à-Brac transcription factors are necessary for formation of functional germline stem cell niches through control of dpp expression in the Drosophila melanogaster ovary

2019 ◽  
Author(s):  
Laurine Miscopein Saler ◽  
Mathieu Bartoletti ◽  
Virginie Hauser ◽  
Anne-Marie Pret ◽  
Laurent Theodore ◽  
...  
Keyword(s):  
Drosophila Melanogaster ◽  
Stem Cell ◽  
Transcription Factors ◽  
Germ Cells ◽  
Primordial Germ Cells ◽  
Somatic Cells ◽  
Bmp Signaling ◽  
Germline Stem Cell ◽  
Larval Stages ◽  
Functional Germline

AbstractMany studies have focused on the mechanisms of stem cell maintenance via their interaction with a particular niche or microenvironment in adult tissues, but how formation of a functional niche is initiated, including how stem cells within a niche are established, is less well understood. Adult Drosophila melanogaster ovary Germline Stem Cell (GSC) niches are comprised of somatic cells forming a stack called a Terminal Filament (TF) and underlying Cap Cells (CCs) and Escort Cells (ECs), which are in direct contact with GSCs. In the adult, the Engrailed (En) transcription factor is specifically expressed in niche cells where it directly controls expression of the decapentaplegic gene (dpp) encoding a member of the Bone Morphogenetic Protein (BMP) family of secreted signaling molecules, which are key factors for GSC maintenance. In late third instar larval ovaries, in response to BMP signaling from newly-formed niches, adjacent primordial germ cells become GSCs. The bric-à-brac paralogs (bab1 and bab2) encode BTB/POZ-domain containing transcription factors, that are also expressed in developing GSCs niches where they are required for TF formation. Here, we demonstrate that Bab1 and Bab2 display redundant cell autonomous function for TF morphogenesis and we identify a new function for these genes in GSC establishment. Moreover, we show that Bab proteins control dpp expression in otherwise correctly specified CCs, independently of En and its paralog Invected (Inv). In fact, our results also indicate that en/inv function in larval stages are neither essential for TF formation, nor GSC establishment. Finally, when bab2 was overexpressed in ovarian somatic cells outside of the niche, where en/inv were not expressed, ectopic BMP signaling activation was induced in adjacent germ cells of adult ovaries, which formed GSC-like tumors. Together, these results indicate that Bab transcription factors are positive regulators of BMP signaling for acquisition of GSC status.

scholarly journals The Bric-à-Brac BTB/POZ transcription factors are necessary in niche cells for germline stem cells establishment and homeostasis through control of BMP/DPP signaling in the Drosophila melanogaster ovary

PLoS Genetics ◽  
2020 ◽  
Vol 16 (11) ◽  
pp. e1009128
Author(s):  
Laurine Miscopein Saler ◽  
Virginie Hauser ◽  
Mathieu Bartoletti ◽  
Charlotte Mallart ◽  
Marianne Malartre ◽  
...  
Keyword(s):  
Stem Cells ◽  
Drosophila Melanogaster ◽  
Stem Cell ◽  
Transcription Factors ◽  
Germ Cells ◽  
Somatic Cells ◽  
Bmp Signaling ◽  
Germline Stem Cell ◽  
Larval Stages ◽  
Adult Ovary

Many studies have focused on the mechanisms of stem cell maintenance via their interaction with a particular niche or microenvironment in adult tissues, but how formation of a functional niche is initiated, including how stem cells within a niche are established, is less well understood. Adult Drosophila melanogaster ovary Germline Stem Cell (GSC) niches are comprised of somatic cells forming a stack called a Terminal Filament (TF) and associated Cap and Escort Cells (CCs and ECs, respectively), which are in direct contact with GSCs. In the adult ovary, the transcription factor Engrailed is specifically expressed in niche cells where it directly controls expression of the decapentaplegic (dpp) gene encoding a member of the Bone Morphogenetic Protein (BMP) family of secreted signaling molecules, which are key factors for GSC maintenance. In larval ovaries, in response to BMP signaling from newly formed niches, adjacent primordial germ cells become GSCs. The bric-à-brac paralogs (bab1 and bab2) encode BTB/POZ domain-containing transcription factors that are expressed in developing niches of larval ovaries. We show here that their functions are necessary specifically within precursor cells for TF formation during these stages. We also identify a new function for Bab1 and Bab2 within developing niches for GSC establishment in the larval ovary and for robust GSC maintenance in the adult. Moreover, we show that the presence of Bab proteins in niche cells is necessary for activation of transgenes reporting dpp expression as of larval stages in otherwise correctly specified Cap Cells, independently of Engrailed and its paralog Invected (En/Inv). Moreover, strong reduction of engrailed/invected expression during larval stages does not impair TF formation and only partially reduces GSC numbers. In the adult ovary, Bab proteins are also required for dpp reporter expression in CCs. Finally, when bab2 was overexpressed at this stage in somatic cells outside of the niche, there were no detectable levels of ectopic En/Inv, but ectopic expression of a dpp transgene was found in these cells and BMP signaling activation was induced in adjacent germ cells, which produced GSC-like tumors. Together, these results indicate that Bab transcription factors are positive regulators of BMP signaling in niche cells for establishment and homeostasis of GSCs in the Drosophila ovary.

Multipotential ability of primitive germ cells from neonatal pig testis cultured in vitro

2009 ◽  
Vol 21 (5) ◽  
pp. 696 ◽  
Author(s):  
Sandeep Goel ◽  
Mayako Fujihara ◽  
Kazuo Tsuchiya ◽  
Yuji Takagi ◽  
Naojiro Minami ◽  
...  
Keyword(s):  
Stem Cell ◽  
Transcription Factors ◽  
Germ Cells ◽  
Cultured Cells ◽  
Primordial Germ Cells ◽  
Primary Cultures ◽  
Cell Potential ◽  
Neonatal Pig ◽  
Stem Cell Potential

Gonocytes are progenitor-type germ cells that arise from primordial germ cells and differentiate further into spermatogonia, thereby initiating spermatogenesis. In the present study, freshly isolated gonocytes were found to have either weak or no expression of pluripotency determining transcription factors, such as POU5F1, SOX2 and C-MYC. Interestingly, the expression of these transcription factors, as well as other vital transcription factors, such as NANOG, KLF4 and DAZL, were markedly upregulated in cultured cells. Cells in primary cultures expressed specific germ cell and pluripotency markers, such as lectin Dolichos biflorus agglutinin (DBA), KIT, ZBTB16, stage-specific embryonic antigen (SSEA-1), NANOG and POU5F1. Using a monoclonal antibody to specifically identify porcine germ cells, the stem cell potential of fresh and cultured cells was determined with a testis xenotransplantation assay. Colonised porcine germ cells were detected only in mouse testes that were either transplanted with fresh testicular cells or with cells from primary cultures. Interestingly, testes transplanted with cells from primary cultures showed colonisation of germ cells in the interstitial space, reflecting their tumourigenic nature. The formation of teratomas with tissues originating from the three germinal layers following the subcutaneous injection of cells into nude mice from primary cultures confirmed their multipotency. The results of the present study may provide useful information for the establishment of multipotent germ stem cell lines from neonatal pig testis.

scholarly journals Smad-Independent BMP Signaling in Somatic Cells Limits the Size of the Germline Stem Cell Pool

2018 ◽  
Vol 11 (3) ◽  
pp. 811-827 ◽  
Author(s):  
Chen-Yuan Tseng ◽  
Yu-Han Su ◽  
Shun-Min Yang ◽  
Kun-Yang Lin ◽  
Chun-Ming Lai ◽  
...  
Keyword(s):  
Stem Cell ◽  
Somatic Cells ◽  
Bmp Signaling ◽  
Germline Stem Cell ◽  
Cell Pool ◽  
Stem Cell Pool

scholarly journals The Wnt pathway limits BMP signaling outside of the germline stem cell niche in Drosophila ovaries

2016 ◽  
Vol 417 (1) ◽  
pp. 50-62 ◽  
Author(s):  
Violaine I. Mottier-Pavie ◽  
Victor Palacios ◽  
Susan Eliazer ◽  
Shane Scoggin ◽  
Michael Buszczak
Keyword(s):  
Stem Cell ◽  
Stem Cell Niche ◽  
Wnt Pathway ◽  
Bmp Signaling ◽  
Germline Stem Cell ◽  
Cell Niche ◽  
Germline Stem Cell Niche

Stem cell factor protects germ cells from apoptosis in vitro

2000 ◽  
Vol 113 (1) ◽  
pp. 161-168 ◽  
Author(s):  
W. Yan ◽  
J. Suominen ◽  
J. Toppari
Keyword(s):  
Stem Cell ◽  
Germ Cells ◽  
Stem Cell Factor ◽  
Primordial Germ Cells ◽  
Survival Function ◽  
Seminiferous Tubules ◽  
Testicular Development ◽  
Dna Laddering ◽  
Survival Effect

Stem cell factor (SCF) plays an important role in migration, adhesion, proliferation, and survival of primordial germ cells and spermatogonia during testicular development. However, the function of SCF in the adult testis is poorly described. We have previously shown that, in the presence of SCF, there were more type A spermatogonia incorporating thymidine at stage XII of rat seminiferous tubules cultured in vitro than in the absence of SCF, implying that the increased DNA synthesis might result from enhanced survival of spermatogonia. To explore the potential pro-survival function of SCF during spermatogenesis, the seminiferous tubules from stage XII were cultured in the presence or absence of SCF (100 ng/ml) for 8, 24, 48, and 72 hours, respectively, and apoptosis was analyzed by DNA laddering and in situ 3′-end labeling (ISEL) staining. Surprisingly, not only spermatogonia, but also spermatocytes and spermatids, were protected from apoptosis in the presence of SCF. Apoptosis took place much later and was less severe in the SCF-treated tubules than in the controls. Based on previous studies showing that FSH prevents germ cells from undergoing apoptosis in vitro, and that SCF level is increased dramatically in response to FSH stimulation, we also tested if the pro-survival effect of FSH is mediated through SCF by using a function-blocking monoclonal antibody, ACK-2, to block SCF/c-kit interaction. After 24 hours of blockade, the protective effect of FSH was partially abolished, as manifested by DNA laddering and ISEL analyses. The present study demonstrates that SCF acts as an important survival factor for germ cells in the adult rat testis and FSH pro-survival effect on germ cells is mediated partially through the SCF/c-kit pathway.

scholarly journals dSETDB1 and SU(VAR)3–9 Sequentially Function during Germline-Stem Cell Differentiation in Drosophila melanogaster

PLoS ONE ◽  
2008 ◽  
Vol 3 (5) ◽  
pp. e2234 ◽  
Author(s):  
Jeongheon Yoon ◽  
Kyu-Sun Lee ◽  
Jung Sun Park ◽  
Kweon Yu ◽  
Sang-Gi Paik ◽  
...  
Keyword(s):  
Drosophila Melanogaster ◽  
Stem Cell ◽  
Cell Differentiation ◽  
Stem Cell Differentiation ◽  
Germline Stem Cell

scholarly journals Control of lateral migration and germ cell elimination by the Drosophila melanogaster lipid phosphate phosphatases Wunen and Wunen 2

2005 ◽  
Vol 171 (4) ◽  
pp. 675-683 ◽  
Author(s):  
Hiroko Sano ◽  
Andrew D. Renault ◽  
Ruth Lehmann
Keyword(s):  
Drosophila Melanogaster ◽  
Axon Guidance ◽  
Germ Cells ◽  
Primordial Germ Cells ◽  
Lateral Migration ◽  
Migration Process ◽  
The Central Nervous System ◽  
Lipid Phosphate ◽  
Lipid Phosphate Phosphatases ◽  
Single Cluster

In most organisms, primordial germ cells (PGCs) arise far from the region where somatic gonadal precursors (SGPs) are specified. Although PGCs in general originate as a single cluster of cells, the somatic parts of the gonad form on each site of the embryo. Thus, to reach the gonad, PGCs not only migrate from their site of origin but also split into two groups. Taking advantage of high-resolution real-time imaging, we show that in Drosophila melanogaster PGCs are polarized and migrate directionally toward the SGPs, avoiding the midline. Unexpectedly, neither PGC attractants synthesized in the SGPs nor known midline repellents for axon guidance were required to sort PGCs bilaterally. Repellent activity provided by wunen (wun) and wunen-2 (wun-2) expressed in the central nervous system, however, is essential in this migration process and controls PGC survival. Our results suggest that expression of wun/wun-2 repellents along the migratory paths provides faithful control over the sorting of PGCs into two gonads and eliminates PGCs left in the middle of the embryo.

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