Germ line differentiation factor Bag of Marbles is a regulator of hematopoietic progenitor maintenance during <i>Drosophila</i> hematopoiesis

Tokusumi, Tsuyoshi; Tokusumi, Yumiko; Hopkins, Dawn W.; Shoue, Douglas A.; Corona, Lauren E.; Schulz, Robert A.

doi:10.1242/dev.069336

Cited by 31 publications

(54 citation statements)

References 29 publications

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“…3G,H). Moreover, expression of an Hh-GFP reporter line (Tokusumi et al, 2011) was observed in all the PSC cells expressing either PI3K caax or TSC1 RNAi, suggesting that increased PSC size is associated with increased production of this inhibitor of prohemocyte differentiation 1715 RESEARCH REPORT Insulin/TOR in hematopoiesis Mandal et al, 2007). Together, our results indicate that increased IIS/TOR signaling not only supports Drosophila hematopoietic niche growth but also promotes its activity.…”

Section: Control Of Hematopoietic Niche Size By Iis and Tor Signalingmentioning

confidence: 67%

“…Notably, in contrast to what we observed in Pten larvae, increased PSC size has been associated with decreased differentiation (Mandal et al, 2007;Sinenko et al, 2009;Tokusumi et al, 2011). We thus assessed the effect of increased IIS/TOR signaling in the PSC on hemocyte differentiation.…”

Section: Control Of Hematopoietic Niche Size By Iis and Tor Signalingmentioning

confidence: 71%

“…The following fly stocks were used: Pcol85-Gal4, UAS::mCD8-GFP (Krzemien et al, 2007) referred here as col-Gal4, ppl-Gal4/CyOGal80; slif Anti , ppl-Gal4/CyO (Colombani et al, 2003), PTEN 100 /CyO Act-GFP, PTEN 117 /CyO Act-GFP (Oldham et al, 2002), UAS::TSC1, UAS::TSC2 (Tapon et al, 2001), UAS::PTEN (Huang et al, 1999), UAS::PI3K caax /Cyo (Leevers et al, 1996), UAS::dFoxo (Puig et al, 2003), tepIV-Gal4 (AvetRochex et al, 2010, Cg25C-GFP and Bc-GFP (Sorrentino et al, 2007), Hh-GFP (Tokusumi et al, 2011). The RNAi stocks were obtained from Vienna Drosophila RNAi Center (VDRC).…”

Section: Drosophila Strains and Larvae Collectionsmentioning

confidence: 99%

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Dual role for Insulin/TOR signaling in the control of hematopoietic progenitor maintenance in Drosophila

et al. 2012

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The interconnected Insulin/IGF signaling (IlS) and Target of Rapamycin (TOR) signaling pathways constitute the main branches of the nutrient-sensing system that couples growth to nutritional conditions in Drosophila. Here, we addressed the influence of these pathways and of diet restriction on the balance between the maintenance of multipotent hematopoietic progenitors and their differentiation in the Drosophila lymph gland. In this larval hematopoietic organ, a pool of stem-like progenitor blood cells (prohemocytes) is kept undifferentiated in response to signaling from a specialized group of cells forming the posterior signaling center (PSC), which serves as a stem cell niche. We show that, reminiscent of the situation in human, loss of the negative regulator of IIS Pten results in lymph gland hyperplasia, aberrant blood cell differentiation and hematopoietic progenitor exhaustion. Using site-directed loss- and gain-of-function analysis, we demonstrate that components of the IIS/TOR pathways control lymph gland homeostasis at two levels. First, they cell-autonomously regulate the size and activity of the hematopoietic niche. Second, they are required within the prohemocytes to control their growth and maintenance. Moreover, we show that diet restriction or genetic alteration mimicking amino acid deprivation triggers progenitor cell differentiation. Hence, our study highlights the role of the IIS/TOR pathways in orchestrating hematopoietic progenitor fate and links blood cell fate to nutritional status.

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Section: Control Of Hematopoietic Niche Size By Iis and Tor Signalingmentioning

confidence: 67%

Section: Control Of Hematopoietic Niche Size By Iis and Tor Signalingmentioning

confidence: 71%

Section: Drosophila Strains and Larvae Collectionsmentioning

confidence: 99%

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Dual role for Insulin/TOR signaling in the control of hematopoietic progenitor maintenance in Drosophila

et al. 2012

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“…Therefore, our data provide a new line of evidence showing distinct molecular mechanisms employed in male versus female germline stem cell differentiation pathways. However, in the lymph gland, Bam maintains hematopoietic progenitors at an undifferentiated state and bam mutation results in a reduction of hematopoietic progenitors, but an increase in differentiated hemocytes (Tokusumi et al, 2011). Therefore, in different tissues, Bam acts differently to either block or induce differentiation.…”

Section: Research Articlementioning

confidence: 99%

“…In addition, as readout for decreased Bam protein levels, we used the percentage of testes containing at least one 32-spermatocyte cyst, which reflects Bam protein levels precisely (Insco et al, 2009); the previous study used nuclear morphology (Pek et al, 2009). In hematopoietic progenitors, Bam and miR-7 function cooperatively, but bam is not a target of miR-7 (Tokusumi et al, 2011).…”

Section: Post-transcriptional Regulation Of Bam By Micrornasmentioning

confidence: 99%

MicroRNAs downregulate Bag of marbles to ensure proper terminal differentiation in the Drosophila male germline

et al. 2013

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SUMMARYIn many adult stem cell lineages, the continuous production of functional differentiated cells depends on the maintenance of progenitor cells in an undifferentiated and proliferative state, as well as the subsequent commitment to proper terminal differentiation. In the Drosophila male germline stem cell (GSC) lineage, a key differentiation factor, Bag of marbles (Bam), is required for the transition from proliferative spermatogonia to differentiating spermatocytes. We show that bam mRNA, but not Bam, is present in spermatocytes, suggesting that bam is regulated post-transcriptionally. Consistent with this, repression of Bam accumulation is achieved by microRNAs via the bam 3ЈUTR. When the bam 3ЈUTR was substituted with the 3ЈUTR of a constitutively expressed -Tubulin, Bam became stabilized in spermatocytes. Moreover, such a persistent expression of Bam in spermatocytes was recapitulated by specifically mutating the putative miR-275/miR-306 recognition site at the bam 3ЈUTR. In addition, overexpression of miR-275 or miR-306 in spermatogonial cells resulted in a delay of the proliferation-to-differentiation transition and resembled the bam loss-of-function phenotype, suggesting that these microRNAs are sufficient to downregulate Bam. Finally, the failure of Bam downregulation in spermatocytes affected spermatid terminal differentiation and resulted in increased male sterility. Our results demonstrate that microRNAs control the stem cell differentiation pathway through regulating Bam, the downregulation of which is crucial for proper spermatid terminal differentiation.

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Drosophilahematopoiesis under normal conditions and in response to immune stress

et al. 2016

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The emergence of hematopoietic progenitors and their differentiation into various highly specialized blood cell types constitute a finely tuned process. Unveiling the genetic cascades that control blood cell progenitor fate and understanding how they are modulated in response to environmental changes are two major challenges in the field of hematopoiesis. In the last 20 years, many studies have established important functional analogies between blood cell development in vertebrates and in the fruit fly, Drosophila melanogaster. Thereby, Drosophila has emerged as a powerful genetic model for studying mechanisms that control hematopoiesis during normal development or in pathological situations. Moreover, recent advances in Drosophila have highlighted how intricate cell communication networks and microenvironmental cues regulate blood cell homeostasis. They have also revealed the striking plasticity of Drosophila mature blood cells and the presence of different sites of hematopoiesis in the larva. This review provides an overview of Drosophila hematopoiesis during development and summarizes our current knowledge on the molecular processes controlling larval hematopoiesis, both under normal conditions and in response to an immune challenge, such as wasp parasitism.

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Germ line differentiation factor Bag of Marbles is a regulator of hematopoietic progenitor maintenance during Drosophila hematopoiesis

Cited by 31 publications

References 29 publications

Dual role for Insulin/TOR signaling in the control of hematopoietic progenitor maintenance in Drosophila

Dual role for Insulin/TOR signaling in the control of hematopoietic progenitor maintenance in Drosophila

MicroRNAs downregulate Bag of marbles to ensure proper terminal differentiation in the Drosophila male germline

Drosophilahematopoiesis under normal conditions and in response to immune stress

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