Opposing JAK-STAT and Wnt signaling gradients define a stem cell domain by regulating differentiation at two borders DOI Creative Commons
David Melamed, Daniel Kalderon

eLife, Journal Year: 2020, Volume and Issue: 9

Published: Nov. 2, 2020

Many adult stem cell communities are maintained by population asymmetry, where stochastic behaviors of multiple individual cells collectively result in a balance between division and differentiation. We investigated how this is achieved for Drosophila Follicle Stem Cells (FSCs) spatially-restricted niche signals. FSCs produce transit-amplifying (FCs) from their posterior face quiescent Escort (ECs) to anterior. show that JAK-STAT pathway activity, which declines anterior, dictates the pattern divisions over FSC domain, promotes more locations conversion FCs, while opposing EC production. Wnt activity anterior production, opposes FC The pathways combine define domain through concerted effects on differentiation ECs FCs at either end signaling gradients, impose proliferation matches derivative production.Adult organisms contain variety routinely replaced using can generate specific tissue. These often clustered into small groups, combinations chemical signals nearby encourage each divide or ‘differentiate’ another type cell. different must somehow maintain size shape community. ovary an fruit fly contains group called follicle cells, short. support continual production eggs supplying two types opposite faces cluster: dividing emerge back cluster guide late egg development, non-dividing escort come front early development. Two control graded cluster. strongest territory gradually towards front, absent cells. However, it was unclear gradients these formation To answer question, Melamed Kalderon used genetic engineering modify strength experiments measured affected rate converted found dictated rates, may explain why varies across do not all. also stimulated become opposed Conversely, stronger favored inhibited transitioning This suggests relative helps thecorrect number balancing JAK-STAT, other development many organisms, including humans, have been linked cancer. Therefore, principles mechanisms uncovered apply Furthermore, work highlights changes allow mutant amplify take entire community, play role cancer illnesses.

Language: Английский

A single-cell atlas and lineage analysis of the adult Drosophila ovary DOI Creative Commons
Katja Rust, Lauren Byrnes, Kevin Shengyang Yu

et al.

Nature Communications, Journal Year: 2020, Volume and Issue: 11(1)

Published: Nov. 6, 2020

The Drosophila ovary is a widely used model for germ cell and somatic tissue biology. Here we use single-cell RNA-sequencing (scRNA-seq) to build comprehensive atlas of the adult that contains transcriptional profiles every major type in ovary, including germline stem cells their niche cells, follicle previously undescribed subpopulations escort cells. In addition, identify Gal4 lines with specific expression patterns perform lineage tracing We discover distinct subpopulation able convert response starvation or upon genetic manipulation, knockdown escargot, overactivation mTor Toll signalling.

Language: Английский

Citations

120
Coordinating Proliferation, Polarity, and Cell Fate in the Drosophila Female Germline DOI Creative Commons
Taylor D. Hinnant, Julie A. Merkle, Elizabeth T. Ables

et al.

Frontiers in Cell and Developmental Biology, Journal Year: 2020, Volume and Issue: 8

Published: Feb. 4, 2020

Gametes are highly specialized cell types produced by a complex differentiation process. Production of viable oocytes requires series precise and coordinated molecular events. Early in their development, germ cells an interconnected group mitotically dividing cells. Key regulatory events lead to the specification mature initiate switch meiotic cycle program. Though chromosomal meiosis have been extensively studied, it is unclear how other aspects oocyte temporally coordinated. The fruit fly, Drosophila melanogaster, has long at forefront as model system for genetics biology research. adult ovary continuously produces throughout organism's lifetime, many cellular processes that occur establish fate conserved with mammalian gamete development. Here, we review recent discoveries from advance our understanding early balance mitotic exit initiation. We discuss control establishment polarity major themes specification. also highlight germline-specific organelle, fusome, integral coordination division, polarity, ovarian Finally, controls might be integrated maintain production.

Language: Английский

Citations

99
A single-cell atlas of the developing Drosophila ovary identifies follicle stem cell progenitors DOI Open Access
Maija Slaidina, Torsten U. Banisch,

Selena Gupta

et al.

Genes & Development, Journal Year: 2020, Volume and Issue: 34(3-4), P. 239 - 249

Published: Jan. 9, 2020

Addressing the complexity of organogenesis at a system-wide level requires complete understanding adult cell types, their origin, and precursor relationships. The

Language: Английский

Citations

80
Wnt6 maintains anterior escort cells as an integral component of the germline stem cell niche DOI Creative Commons
Xiaoxi Wang, Andrea Page-McCaw

Development, Journal Year: 2018, Volume and Issue: unknown

Published: Jan. 1, 2018

Stem cells reside in a niche, complex cellular and molecular environment. In Drosophila ovaries, germline stem depend on cap for self-renewing signals physical attachment. Germline also contact the anterior escort cells, here we report that are absolutely required cell maintenance. When die from impaired Wnt signaling or hid expression, loss of causes consequent cells. Anterior function as an integral niche component by promoting DE-cadherin anchorage transiently expressing Dpp ligand to promote full-strength BMP maintained Wnt6 ligands produced cells; without signaling, leaving vacancies leading Our data identify constituents cap-cell survival signal.

Language: Английский

Citations

62
<p>New Advances in Canonical Wnt/β-Catenin Signaling in Cancer</p> DOI Creative Commons

Xiaolan Wen,

Yanling Wu, Annoor Awadasseid

et al.

Cancer Management and Research, Journal Year: 2020, Volume and Issue: Volume 12, P. 6987 - 6998

Published: Aug. 1, 2020

Abstract: Wnt/β-catenin-mediated signaling is a key pathway regulating tissue growth and development, tumorigenesis, has received increasing attention in recent years. In addition to participating healthy organ ectopic activation of the can cause variety tumors other pathologies. The plays critical role many processes such as proliferation, differentiation, apoptosis, migration, invasion, epithelial–mesenchymal transition cancer cell stemness. importance Wnt signal self-evident. This review describes underlying mechanism highlights latest findings on relationship between tumorigenesis. addition, potential miRNAs presented. Furthermore, we discuss intrinsic link stemness, which shed light malignant progression tumor cells. Finally, treatment strategies based canonical are summarized, hoping help clinical development. Keywords: Wnt/β-catenin, tumor, miRNAs, stem cell, target, therapeutic strategy

Language: Английский

Citations

57
A single-cell atlas reveals unanticipated cell type complexity in Drosophila ovaries DOI Creative Commons
Maija Slaidina,

Selena Gupta,

Torsten U. Banisch

et al.

Genome Research, Journal Year: 2021, Volume and Issue: 31(10), P. 1938 - 1951

Published: Aug. 13, 2021

Organ function relies on the spatial organization and functional coordination of numerous cell types. The Drosophila ovary is a widely used model system to study cellular activities underlying organ function, including stem regulation, signaling epithelial morphogenesis. However, relative paucity type–specific reagents hinders investigation molecular functions at appropriate resolution. Here, we single-cell RNA sequencing characterize all types compartment early follicles ovary. We computed transcriptional signatures identified specific markers for nine states germ differentiation 23 somatic subtypes. uncovered an unanticipated diversity escort cells, cells that directly interact with differentiating germline cysts. Three subtypes reside in discrete anatomical positions express distinct sets secreted transmembrane proteins, suggesting diverse micro-environments support progressive cells. Finally, 17 follicle characterized their profiles. Altogether, provide comprehensive resource gene expression, markers, coordinates, predictions 34 ovarian

Language: Английский

Citations

52
Quantitative microscopy of the Drosophila ovary shows multiple niche signals specify progenitor cell fate DOI Creative Commons
Wei Dai, Amy Peterson, Thomas Kenney

et al.

Nature Communications, Journal Year: 2017, Volume and Issue: 8(1)

Published: Oct. 26, 2017

Abstract Adult stem cells commonly give rise to transit-amplifying progenitors, whose progeny differentiate into distinct cell types. It is unclear if niche signals coordinate fate decisions within the progenitor pool. Here we use quantitative analysis of Wnt, Hh, and Notch signalling reporters markers Eyes Absent (Eya) Castor (Cas) study effects hyper-activation loss on development in Drosophila ovary. Follicle (FSC) adopt polar, stalk, main body fates. We show that Wnt transiently inhibits expression determinant Eya, hyperactivity strongly biases towards polar stalk Hh independently controls proliferation differentiation transition. permissive but not instructive for multiple These findings reveal fates cells.

Language: Английский

Citations

44
Wnt Signaling in Stem Cell Maintenance and Differentiation in the Drosophila Germarium DOI Open Access
Indrayani Waghmare, Andrea Page-McCaw

Genes, Journal Year: 2018, Volume and Issue: 9(3), P. 127 - 127

Published: Feb. 27, 2018

Wnt signaling is a conserved regulator of stem cell behaviors, and the Drosophila germarium has been an important model tissue for study maintenance, differentiation, proliferation. Here we review in germarium, which houses two distinct types ovarian cells: anteriorly located germline cells (GSCs), give rise to oocytes; mid-posteriorly follicle (FSCs), somatic that cover developing oocyte. The maintenance proliferation GSCs FSCs regulated by niches, whereas differentiation niche. Four ligands are localized focus on how these affects both their respective niches.

Language: Английский

Citations

43
The follicle epithelium in the Drosophila ovary is maintained by a small number of stem cells DOI Creative Commons

Jocelyne Fadiga,

Todd Nystul

eLife, Journal Year: 2019, Volume and Issue: 8

Published: Dec. 18, 2019

The follicle stem cells (FSCs) in the Drosophila ovary are an important experimental model for study of epithelial cell biology. Although decades research support conclusion that there two FSCs per ovariole, a recent used novel clonal marking system to conclude 15-16 ovariole. We performed analysis using both this and standard systems, identified several problems may have contributed overestimate FSC number. In addition, we developed new methods accurately measuring clone size, found clones produce, on average, half each Our findings provide strong independent typically active though they consistent with up four germarium.

Language: Английский

Citations

40
Wingless/Wnt Signaling in Intestinal Development, Homeostasis, Regeneration and Tumorigenesis: A Drosophila Perspective DOI Creative Commons

Ai Tian,

Hassina Benchabane, Yashi Ahmed

et al.

Journal of Developmental Biology, Journal Year: 2018, Volume and Issue: 6(2), P. 8 - 8

Published: March 28, 2018

In mammals, the Wnt/β-catenin signal transduction pathway regulates intestinal stem cell maintenance and proliferation, whereas Wnt hyperactivation, resulting primarily from inactivation of tumor suppressor Adenomatous polyposis coli (APC), triggers development vast majority colorectal cancers. The Drosophila adult gut has recently emerged as a powerful model to elucidate mechanisms by which Wingless/Wnt signaling development, homeostasis, regeneration, tumorigenesis. Herein, we review recent insights on roles in physiology pathology.

Language: Английский

Citations

39