Feedback Inhibition of JAK/STAT Signaling by Apontic Is Required to Limit an Invasive Cell Population

Starz‐Gaiano, Michelle; Melani, Mariana; Wang, Xiaobo; Meinhardt, Hans; Montell, Denise J.

doi:10.1016/j.devcel.2008.03.005

Cited by 77 publications

(146 citation statements)

References 40 publications

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“…1G,J,K) suggests that JAK/STAT signalling might be affected. To further investigate the role of MT or Dynein in oBC specification through JAK/STAT signalling we used the 10ϫSTAT92EGFP reporter line, which accurately reflects JAK/STAT activity (Bach et al, 2007;Starz-Gaiano et al, 2008). At stage 8, GFP accumulates in the nuclei of follicular cells surrounding the PCs in a graded manner.…”

Section: Jak/stat Signalling Is Altered In the Absence Of Dynein Cargmentioning

confidence: 99%

“…The transport of upd mRNA and the subsequent accumulation of the Upd protein apically contribute to setting the high concentration of ligand required for oBC determination. Recently, a new negative-feedback mechanism has been identified in oBCs that involves a regulatory circuit between Slbo, STAT and Apt (Starz-Gaiano et al, 2008;Starz-Gaiano et al, 2009). This feedback mechanism inhibits JAK/STAT activity in cells that receive low levels of Upd ligand, i.e.…”

Section: Research Articlementioning

confidence: 99%

“…These findings suggest that JAK/STAT activity needs to be tightly controlled and that a specific level of signalling must be reached close to the ligand source, allowing the selection of an appropriate number of oBCs. One control mechanism involves the DNA-binding protein Apontic (Apt), which spatially regulates JAK/STAT signalling in the egg chamber follicular epithelium and prevents the recruitment of cells distant from the ligand source (Starz-Gaiano et al, 2008). In addition, it was shown that JAK/STAT activity has to be maintained during the entire process of migration to prevent splitting of the cluster (Silver et al, 2005).…”

Section: Introductionmentioning

confidence: 99%

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Asymmetric localisation of cytokine mRNA is essential for JAK/STAT activation during cell invasiveness

et al. 2011

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SUMMARYThe transition from immotile epithelial cells to migrating cells occurs in all organisms during normal embryonic development, as well as during tumour metastasis. During Drosophila oogenesis, border cells (BCs) are recruited and delaminate from the follicular epithelium. This process is triggered by the polar cells (PCs), which secrete the cytokine Unpaired (Upd) and activate the JAK/STAT pathway in neighbouring cells, turning them into invasive BCs. Interestingly, either a decrease or an increase in BC number alters migration, indicating that mechanisms controlling the level of JAK/STAT signalling are crucial in this process. Here, we show that PCs have a highly stable and polarised network of microtubules along which upd transcripts are asymmetrically transported in a Dynein-dependent manner. We demonstrate that in the absence of upd mRNA localisation the ligand is no longer efficiently secreted, leading to a loss of signalling strength as well as recruitment and migration defects. These findings reveal a novel posttranscriptional regulatory mechanism of JAK/STAT signalling in the control of epithelial cell invasiveness.

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Section: Jak/stat Signalling Is Altered In the Absence Of Dynein Cargmentioning

confidence: 99%

Section: Research Articlementioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Asymmetric localisation of cytokine mRNA is essential for JAK/STAT activation during cell invasiveness

et al. 2011

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“…In addition, a number of studies have reported other genes in which mutant clones were observed to lag behind the cluster, causing a delay in migration (Rorth et al, 2000;Bianco et al, 2007;Starz-Gaiano et al, 2008). In this study, we provide the first example of acceleration of clusters caused by sima or tgo mutations in a single leading cell.…”

Section: Discussionmentioning

confidence: 75%

Dose-dependent modulation of HIF-1α/sima controls the rate of cell migration and invasion in Drosophila ovary border cells

et al. 2009

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The role of the hypoxic response during metastasis was analysed in migrating border cells of the Drosophila ovary. Acute exposure to 1% O 2 delayed or blocked border cell migration (BCM), whereas prolonged exposure resulted in the first documented accelerated BCM phenotype. Similarly, manipulating the expression levels of sima, the Drosophila hypoxia-inducible factor (HIF)-1a ortholog, revealed that Sima can either block or restore BCM in a dose-dependent manner. In contrast, overexpression of Vhl (Drosophila von Hippel-Lindau) generated a range of phenotypes, including blocked, delayed and accelerated BCM, whereas over-expression of hph (Drosophila HIF prolyl hydroxylase) only accelerated BCM. Mosaic clone analysis of sima or tango (HIF-1b ortholog) mutants revealed that cells lacking Hif-1 transcriptional activity were preferentially detected in the leading cell position of the cluster, resulting in either a delay or acceleration of BCM. Moreover, in sima mutant cell clones, there was reduced expression of nuclear slow border cells (Slbo) and basolateral DE-cadherin, proteins essential for proper BCM. These results show that Sima levels define the rate of BCM in part through regulation of Slbo and DE-cadherin, and suggest that dynamic regulation of Hif-1 activity is necessary to maintain invasive potential of migrating epithelial cells.

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“…Reduction of Stat92E activity during the migration process (Silver et al, 2005), as well as its overactivation, interferes with BCC migration (Yoon et al, 2011). Loss of slbo function in rosette cells blocks the motility of the BCC (Montell et al, 1992;Rørth et al, 2000), whereas overexpression of slbo causes a delay in migration and frequently a fragmentation of the BCC (Rørth et al, 2000;Starz-Gaiano et al, 2008). Similarly, not only does lack of DEcad abolish BCC motility (Niewiadomska et al, 1999), but also higher-than-normal expression of DEcad in rosette cells delays migration (Schober et al, 2005).…”

Section: Introductionmentioning

confidence: 99%

The Maf factor Traffic jam both enables and inhibits collective cell migration inDrosophilaoogenesis

2013

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SUMMARYBorder cell cluster (BCC) migration in the Drosophila ovary is an excellent system to study the gene regulatory network that enables collective cell migration. Here, we identify the large Maf transcription factor Traffic jam (Tj) as an important regulator of BCC migration. Tj has a multifaceted impact on the known core cascade that enables BCC motility, consisting of the Jak/Stat signaling pathway, the C/EBP factor Slow border cells (Slbo), and the downstream effector DE-cadherin (DEcad). The initiation of BCC migration coincides with a Slbo-dependent decrease in Tj expression. This reduction of Tj is required for normal BCC motility, as high Tj expression strongly impedes migration. At high concentration, Tj has a tripartite negative effect on the core pathway: a decrease in Slbo, an increase in the Jak/Stat inhibitor Socs36E, and a Slbo-independent reduction of DEcad. However, maintenance of a low expression level of Tj in the BCC during migration is equally important, as loss of tj function also results in a significant delay in migration concomitant with a reduction of Slbo and consequently of DEcad. Taken together, we conclude that the regulatory feedback loop between Tj and Slbo is necessary for achieving the correct activity levels of migration-regulating factors to ensure proper BCC motility.

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Feedback Inhibition of JAK/STAT Signaling by Apontic Is Required to Limit an Invasive Cell Population

Cited by 77 publications

References 40 publications

Asymmetric localisation of cytokine mRNA is essential for JAK/STAT activation during cell invasiveness

Asymmetric localisation of cytokine mRNA is essential for JAK/STAT activation during cell invasiveness

Dose-dependent modulation of HIF-1α/sima controls the rate of cell migration and invasion in Drosophila ovary border cells

The Maf factor Traffic jam both enables and inhibits collective cell migration inDrosophilaoogenesis

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