The Hox Gene Abd-B Controls Stem Cell Niche Function in the Drosophila Testis

Papagiannouli, Fani; Schardt, Lisa; Grajcarek, Janin; Ha, Nati; Lohmann, Ingrid

doi:10.1016/j.devcel.2014.02.004

Cited by 6 publications

(42 citation statements)

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“…Hub positioning and integrity is tightly coupled to adhesion and cell communication, with βPS-Integrin (encoded by the myospheroid (mys) gene) and the Boss/Sev pathway playing key roles in embryonic gonads (Kitadate et al, 2007;Tanentzapf et al, 2007) as well as in larval (Figs. 1B, D-F, 2A-D) (Papagiannouli et al, 2014) and adult testes (Kitadate et al, 2007;Lee et al, 2008;Papagiannouli et al, 2014;Tanentzapf et al, 2007). A similar role in hub positioning and integrity was shown for Lasp in larval (Fig.…”

Section: Resultssupporting

confidence: 61%

“…Yet, we have not observed hub loss in talin depleted larval testes, as it has been reported for talin depleted adult testes (Tanentzapf et al, 2007) (see "Experimental procedures" section for detailed explanation). Throughout this study, normal hub position is expected at the anterior tip of the testis, at the opposite side of the posterior terminal cells, as shown before (Papagiannouli et al, 2014).…”

Section: Resultsmentioning

confidence: 96%

“…In order to prevent the accumulation of cell autonomous and nonautonomous stem cell and spermatogenesis defects, proper function of the stem cell niche has to be secured at subsequent steps of testis organogenesis (Kitadate et al, 2007;Le Bras and Van Doren, 2006;Lee et al, 2008;Papagiannouli et al, 2014;Tanentzapf et al, 2007). Hub positioning and integrity is tightly coupled to adhesion and cell communication, with βPS-Integrin (encoded by the myospheroid (mys) gene) and the Boss/Sev pathway playing key roles in embryonic gonads (Kitadate et al, 2007;Tanentzapf et al, 2007) as well as in larval (Figs.…”

Section: Resultsmentioning

confidence: 99%

“…Sustained activity of Abd-B in pre-meiotic germline spermatocytes of larval testes is required to secure niche positioning and integrity by regulating integrin localization in the neighboring SCCs (Papagiannouli et al, 2014). Identification of direct Abd-B target genes revealed that Abd-B mediates its effects by controlling the activity of the Sev ligand Boss via its direct targets src42A and sec63.…”

Section: Introductionmentioning

confidence: 99%

“…Two SCCs enclose each gonialblast thereby forming a cyst that is "sealed" outside by the extracellular matrix (ECM) (Fig. 1A) (Papagiannouli et al, 2014). The gonialblast divides mitotically four more times to give rise to 16 interconnected spermatogonial cells, which then undergo pre-meiotic DNA replication and become spermatocytes.…”

Section: Introductionmentioning

confidence: 99%

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Stage-specific control of niche positioning and integrity in the Drosophila testis

Schardt

Ander

Lohmann

et al. 2015

Mechanisms of Development

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A fundamental question is how complex structures are maintained after their initial specification. Stem cells reside in a specialized microenvironment, called niche, which provides essential signals controlling stem cell behavior. We addressed this question by studying the Drosophila male stem cell niche, called the hub. Once specified, the hub cells need to maintain their position and architectural integrity through embryonic, larval and pupal stages of testis organogenesis and during adult life. The Hox gene Abd-B, in addition to its described role in male embryonic gonads, maintains the architecture and positioning of the larval hub from the germline by affecting integrin localization in the neighboring somatic cyst cells. We find that the AbdB-Boss/Sev cascade affects integrin independent of Talin, while genetic interactions depict integrin as the central downstream player in this system. Focal adhesion and integrin-adaptor proteins within the somatic stem cells and cyst cells, such as Paxillin, Pinch and Vav, also contribute to proper hub integrity and positioning. During adult stages, hub positioning is controlled by Abd-B activity in the outer acto-myosin sheath, while Abd-B expression in adult spermatocytes exerts no effect on hub positioning and integrin localization. Our data point at a cell- and stage-specific function of Abd-B and suggest that the occurrence of new cell types and cell interactions in the course of testis organogenesis made it necessary to adapt the whole system by reusing the same players for male stem cell niche positioning and integrity in an alternative manner.

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Section: Resultssupporting

confidence: 61%

Section: Resultsmentioning

confidence: 96%

Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Stage-specific control of niche positioning and integrity in the Drosophila testis

Schardt

Ander

Lohmann

et al. 2015

Mechanisms of Development

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Decoding the Regulatory Logic of the Drosophila Male Stem Cell System

et al. 2018

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The niche critically controls stem cell behavior, but its regulatory input at the whole-genome level is poorly understood. We elucidated transcriptional programs of the somatic and germline lineages in the Drosophila testis and genome-wide binding profiles of Zfh-1 and Abd-A expressed in somatic support cells and crucial for fate acquisition of both cell lineages. We identified key roles of nucleoporins and V-ATPase proton pumps and demonstrate their importance in controlling germline development from the support side. To make our dataset publicly available, we generated an interactive analysis tool, which uncovered conserved core genes of adult stem cells across species boundaries. We tested the functional relevance of these genes in the Drosophila testis and intestine and found a high frequency of stem cell defects. In summary, our dataset and interactive platform represent versatile tools for identifying gene networks active in diverse stem cell types.

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Hox5genes direct elastin network formation during alveologenesis by regulating myofibroblast adhesion

Hrycaj

Marty-Santos

Cebrián

et al. 2018

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

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Hox5genes (Hoxa5,Hoxb5,Hoxc5) are exclusively expressed in the lung mesenchyme during embryogenesis, and the most severe phenotypes result from constitutive loss of function of all three genes. BecauseHox5triple null mutants exhibit perinatal lethality, the contribution of this paralogous group to postembryonic lung development is unknown. Intriguingly, expression of all threeHox5genes peaks during the first 2 weeks after birth, reaching levels far exceeding those measured at embryonic stages, and survivingHoxa5single andHox5 AabbCccompound mutants exhibit defects in the localization of alveolar myofibroblasts. To define the contribution of the entireHox5paralogous group to this process, we generated anHoxa5conditional allele to use with our existing null alleles forHoxb5andHoxc5. Postnatally, mesenchymal deletion ofHoxa5in anHoxb5/Hoxc5double-mutant background results in severe alveolar simplification. The elastin network required for alveolar formation is dramatically disrupted inHox5triple mutants, while the basal lamina, interstitial matrix, and fibronectin are normal. Alveolar myofibroblasts remain Pdgfrα+/SMA+ double positive and present in normal numbers, indicating that the irregular elastin network is not due to fibroblast differentiation defects. Rather, we observe that SMA+ myofibroblasts ofHox5triple mutants are morphologically abnormal both in vivo and in vitro with highly reduced adherence to fibronectin. This loss of adhesion is a result of loss of the integrin heterodimer Itga5b1 in mutant fibroblasts. Collectively, these data show an important role forHox5genes in lung fibroblast adhesion necessary for proper elastin network formation during alveologenesis.

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The Hox Gene Abd-B Controls Stem Cell Niche Function in the Drosophila Testis

Cited by 6 publications

References 0 publications

Stage-specific control of niche positioning and integrity in the Drosophila testis

Stage-specific control of niche positioning and integrity in the Drosophila testis

Decoding the Regulatory Logic of the Drosophila Male Stem Cell System

Hox5genes direct elastin network formation during alveologenesis by regulating myofibroblast adhesion

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