Signal transduction pathways, intrinsic regulators, and the control of cell fate choice

Fossett, Nancy

doi:10.1016/j.bbagen.2012.06.005

Cited by 36 publications

(30 citation statements)

References 117 publications

(298 reference statements)

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“…Blood cell production occurs in separate waves during two developmental stages (Evans et al, 2003;Fossett, 2013). The first wave occurs during embryogenesis, with hematopoietic progenitors initially derived from the cephalic mesoderm.…”

Section: Introductionmentioning

confidence: 99%

Bag of Marbles controls the size and organization of the Drosophila hematopoietic niche through interactions with the Insulin-like growth factor pathway and Retinoblastoma-family protein

Tokusumi

Hopkins

et al. 2015

Development

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Bag of Marbles (Bam) is known to function as a positive regulator of hematopoietic progenitor maintenance in the lymph gland blood cell-forming organ during Drosophila hematopoiesis. Here, we demonstrate a key function for Bam in cells of the lymph gland posterior signaling center (PSC), a cellular domain proven to function as a hematopoietic niche. Bam is expressed in PSC cells, and gene loss-of-function results in PSC overgrowth and disorganization, indicating that Bam plays a crucial role in controlling the proper development of the niche. It was previously shown that Insulin receptor (InR) pathway signaling is essential for proper PSC cell proliferation. We analyzed PSC cell number in lymph glands double-mutant for bam and InR pathway genes, and observed that bam genetically interacts with pathway members in the formation of a normal PSC. The elF4A protein is a translation factor downstream of InR pathway signaling, and functional knockdown of this crucial regulator rescued the bam PSC overgrowth phenotype, further supporting the cooperative function of Bam with InR pathway members. Additionally, we documented that the Retinoblastoma-family protein (Rbf), a proven regulator of cell proliferation, was present in cells of the PSC, with a bam functiondependent expression. By contrast, perturbation of Decapentaplegic or Wingless signaling failed to affect Rbf niche cell expression. Together, these findings indicate that InR pathway-Bam-Rbf functional interactions represent a newly identified means to regulate the correct size and organization of the PSC hematopoietic niche.

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Section: Introductionmentioning

confidence: 99%

Bag of Marbles controls the size and organization of the Drosophila hematopoietic niche through interactions with the Insulin-like growth factor pathway and Retinoblastoma-family protein

Tokusumi

Hopkins

et al. 2015

Development

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“…Blood cells arise from a common multipotent progenitor whose development is tightly controlled to allow on the one hand the maintenance of a pool of progenitors and on the other hand the balanced production of the different hematopoietic lineages (1). This equilibrium is controlled both by intrinsic genetically-encoded determinants and by extrinsic cues such as infection (2). Several features of blood cell development and function appear well conserved during evolution and one Drosophila melanogaster larval hematopoietic organ, the lymph gland (LG), has emerged as a powerful model to study in vivo the relationships between multipotent hematopoietic progenitors, their differentiated progeny and regulatory (micro)environmental cues (3).…”

mentioning

confidence: 99%

The EBF transcription factor Collier directly promotes Drosophila blood cell progenitor maintenance independently of the niche

Benmimoun

Polesello

Haenlin

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

149

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The maintenance of stem or progenitor cell fate relies on intrinsic factors as well as local cues from the cellular microenvironment and systemic signaling. In the lymph gland, an hematopoietic organ in Drosophila larva, a group of cells called the Posterior Signaling Centre (PSC), whose specification depends on the EBF transcription factor Collier (Col) and the HOX factor Antennapedia (Antp), has been proposed to form a niche required to maintain the pool of hematopoietic progenitors (prohemocytes). In contrast with this model, we show here that genetic ablation of the PSC does not cause an increase in blood cell differentiation or a loss of blood cell progenitors. Furthermore, although both col and Antp mutant larvae are devoid of PSC, the massive prohemocyte differentiation observed in col mutant is not phenocopied in Antp mutant. Interestingly, beside its expression in the PSC, Col is also expressed at low levels in prohemocytes and we show that this expression persists in PSC-ablated and Antp mutant larvae. Moreover, targeted knockdown and rescue experiments indicate that Col expression is required in the prohemocytes to prevent their differentiation. Together, our findings show that the PSC is dispensable for blood cell progenitor maintenance and reveal the key role of the conserved transcription factor Col as an intrinsic regulator of hematopoietic progenitor fate.hematopoiesis | Drosophila | stem cell niche | EBF

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“…Various lines of experimental evidence suggest that signaling pathways and molecular networks of transcription factors constitute key aspects of stem cell regulation (Orkin and Zon 2008). Functional homologs of many of these signaling pathways and transcription factors are present in Drosophila and mutations in their respective fly genes give rise to hematopoietic defects (Crozatier and Meister 2007;Krzemien et al 2010a;Fossett 2013;Honti et al 2013).…”

mentioning

confidence: 99%

“…Like mammalian macrophages, plasmatocytes engulf bacteria and apoptotic cells and make up the majority of circulating cells. Plasmatocytes and crystal cells circulating in the hemolymph have an embryonic origin and represent a developmental compartment that is distinct from the lymph gland (reviewed in Crozatier and Meister 2007;Fossett 2013). A non-hematopoietic niche, also referred to as the posterior signaling center, located at the base of the anterior lobes maintains progenitor quiescence in the anterior lobes (Lebestky et al 2003;Krzemien et al 2007;Mandal et al 2007).…”

mentioning

confidence: 99%

An Unexpected Link Between Notch Signaling and ROS in Restricting the Differentiation of Hematopoietic Progenitors in Drosophila

et al. 2014

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A fundamental question in hematopoietic development is how multipotent progenitors achieve precise identities, while the progenitors themselves maintain quiescence. In Drosophila melanogaster larvae, multipotent hematopoietic progenitors support the production of three lineages, exhibit quiescence in response to cues from a niche, and from their differentiated progeny. Infection by parasitic wasps alters the course of hematopoiesis. Here we address the role of Notch (N) signaling in lamellocyte differentiation in response to wasp infection. We show that Notch activity is moderately high and ubiquitous in all cells of the lymph gland lobes, with crystal cells exhibiting the highest levels. Wasp infection reduces Notch activity, which results in fewer crystal cells and more lamellocytes. Robust lamellocyte differentiation is induced even in N mutants. Using RNA interference knockdown of N, Serrate, and neuralized (neur), and twin clone analysis of a N null allele, we show that all three genes inhibit lamellocyte differentiation. However, unlike its cell-autonomous function in crystal cell development, Notch's inhibitory influence on lamellocyte differentiation is not cell autonomous. High levels of reactive oxygen species in the lymph gland lobes, but not in the niche, accompany N RNAi -induced lamellocyte differentiation and lobe dispersal. Our results define a novel dual role for Notch signaling in maintaining competence for basal hematopoiesis: while crystal cell development is encouraged, lamellocytic fate remains repressed. Repression of Notch signaling in fly hematopoiesis is important for host defense against natural parasitic wasp infections. These findings can serve as a model to understand how reactive oxygen species and Notch signals are integrated and interpreted in vivo.

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Signal transduction pathways, intrinsic regulators, and the control of cell fate choice

Cited by 36 publications

References 117 publications

Bag of Marbles controls the size and organization of the Drosophila hematopoietic niche through interactions with the Insulin-like growth factor pathway and Retinoblastoma-family protein

Bag of Marbles controls the size and organization of the Drosophila hematopoietic niche through interactions with the Insulin-like growth factor pathway and Retinoblastoma-family protein

The EBF transcription factor Collier directly promotes Drosophila blood cell progenitor maintenance independently of the niche

An Unexpected Link Between Notch Signaling and ROS in Restricting the Differentiation of Hematopoietic Progenitors in Drosophila

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