scholarly journals Musashi regulates follicle stem cell maintenance and epithelial niche homeostasis in the Drosophila ovary

2020 ◽  
Author(s):  
Nicole A. Siddall ◽  
Franca Casagranda ◽  
Nicole Dominado ◽  
James Heaney ◽  
Jessie M. Sutherland ◽  
...  

AbstractThe Musashi (Msi) family of RNA-binding proteins regulate maintenance and differentiation of stem cells in multiple tissues of different species. Here, we use the powerful system of the Drosophila ovary to uncover an intrinsic requirement for Msi in both the maintenance of the follicle stem cell population and regulation of the architecture of the follicle stem cell niche. Further, we demonstrate an associated G2 lag of cycling somatic cells within the niche when Msi function is abrogated. Additionally, we show that Msi interaction with the Wnt pathway influences differentiation of anterior germarial escort cells from cells within the follicle stem cell niche region. This provides further evidence that escort cells can be derived from follicle stem/precursor cells and that Msi regulates lineage differentiation of follicle stem cell daughters.

2016 ◽  
Vol 417 (1) ◽  
pp. 50-62 ◽  
Author(s):  
Violaine I. Mottier-Pavie ◽  
Victor Palacios ◽  
Susan Eliazer ◽  
Shane Scoggin ◽  
Michael Buszczak

2017 ◽  
Vol 114 (15) ◽  
pp. 4005-4010 ◽  
Author(s):  
Yuting Liu ◽  
Meizhi Xu ◽  
Nengsong Liang ◽  
Yanghang Zheng ◽  
Qiaozhi Yu ◽  
...  

Stem cells serve as the source of new cells for plant development. A group of stem cells form a stem cell niche (SCN) at the root tip and in the center of the SCN are slowly dividing cells called the quiescent center (QC). QC is thought to function as a signaling hub that inhibits differentiation of surrounding stem cells. Although it has been generally assumed that cell-to-cell communication provides positional information for QC and SCN maintenance, the tools for testing this hypothesis have long been lacking. Here we exploit a system that effectively blocks plasmodesmata (PD)-mediated signaling to explore how cell-to-cell communication functions in the SCN. We showed that the symplastic signaling between the QC and adjacent cells directs the formation of local auxin maxima and establishment of AP2-domain transcription factors, PLETHORA gradients. Interestingly we found symplastic signaling is essential for local auxin biosynthesis, which acts together with auxin polar transport to provide the guidance for local auxin enrichment. Therefore, we demonstrate the crucial role of cell-to-cell communication in the SCN maintenance and further uncover a mechanism by which symplastic signaling initiates and reinforces the positional information during stem cell maintenance via auxin regulation.


2016 ◽  
Vol 215 (3) ◽  
pp. 401-413 ◽  
Author(s):  
Maryam Yousefi ◽  
Ning Li ◽  
Angela Nakauka-Ddamba ◽  
Shan Wang ◽  
Kimberly Davidow ◽  
...  

Regeneration of the intestinal epithelium is driven by multiple intestinal stem cell (ISC) types, including an active, radiosensitive Wnthigh ISC that fuels turnover during homeostasis and a reserve, radioresistant Wntlow/off ISC capable of generating active Wnthigh ISCs. We examined the role of the Msi family of oncoproteins in the ISC compartment. We demonstrated that Msi proteins are dispensable for normal homeostasis and self-renewal of the active ISC, despite their being highly expressed in these cells. In contrast, Msi proteins are required specifically for activation of reserve ISCs, where Msi activity is both necessary and sufficient to drive exit from quiescence and entry into the cell cycle. Ablation of Msi activity in reserve ISCs rendered the epithelium unable to regenerate in response to injury that ablates the active stem cell compartment. These findings delineate a molecular mechanism governing reserve ISC quiescence and demonstrate a necessity for the activity of this rare stem cell population in intestinal regeneration.


Author(s):  
Kasun Buddika ◽  
Jingjing Xu ◽  
Ishara S. Ariyapala ◽  
Nicholas S. Sokol

AbstractThe adult Drosophila intestinal epithelium is a model system for stem cell biology, but its utility is limited by current biochemical methods that lack cell type resolution. Here, we describe a new proximity-based profiling method that relies upon a GAL4 driver, termed intestinal-kickout-GAL4 (I-KCKT-GAL4), exclusively expressed in intestinal progenitor cells. This method used UV cross-linked whole animal frozen powder as its starting material to immunoprecipitate the RNA cargoes of transgenic epitope-tagged RNA binding proteins driven by I-KCKT-GAL4. When applied to the general mRNA-binder, poly(A)-binding protein, the RNA profile obtained by this method identified 98.8% of transcripts found after progenitor cell sorting, and had low background noise despite being derived from whole animal lysate. We also mapped the targets of the more selective RNA binder, Fragile Mental Retardation Protein, using enhanced CLIP, and report for the first time its binding motif in Drosophila cells. This method will therefore enable the RNA profiling of wildtype and mutant intestinal progenitor cells from intact flies exposed to normal and altered environments, as well as the identification of RNA-protein interactions critical for stem cell function.Summary StatementWe report a dissection-free method to identify proximity-based RNA-protein interactions in an in vivo stem cell population, enabling molecular analysis of these cells at unprecedented speed and resolution.


2016 ◽  
Vol 19 (2) ◽  
pp. 205-216 ◽  
Author(s):  
Carmen Dominguez-Brauer ◽  
Zhenyue Hao ◽  
Andrew J. Elia ◽  
Jérôme M. Fortin ◽  
Robert Nechanitzky ◽  
...  

PLoS Genetics ◽  
2016 ◽  
Vol 12 (1) ◽  
pp. e1005763 ◽  
Author(s):  
John R. Pearson ◽  
Federico Zurita ◽  
Laura Tomás-Gallardo ◽  
Alfonsa Díaz-Torres ◽  
María del Carmen Díaz de la Loza ◽  
...  

2015 ◽  
Author(s):  
Vincent L. Cannataro ◽  
Scott A. McKinley ◽  
Colette M. St. Mary

Somatic tissue evolves over a vertebrate's lifetime due to the accumulation of mutations in stem cell populations. Mutations may alter cellular fitness and contribute to tumorigenesis or aging. The distribution of mutational effects within somatic cells is not known. Given the unique regulatory regime of somatic cell division we hypothesize that mutational effects in somatic tissue fall into a different framework than whole organisms; one in which there are more mutations of large effect. Through simulation analysis we investigate the fit of tumor incidence curves generated using exponential and power law Distributions of Fitness Effects (DFE) to known tumorigenesis incidence. Modeling considerations include the architecture of stem cell populations, i.e., a large number of very small populations, and mutations that do and do not fix neutrally in the stem cell niche. We find that the typically quantified DFE in whole organisms is sufficient to explain tumorigenesis incidence. Further, due to the effects of small stem cell population sizes, i.e., strong genetic drift, deleterious mutations are predicted to accumulate, resulting in reduced tissue maintenance. Thus, despite there being a large number of stem cells throughout the intestine, its compartmental architecture leads to significant aging, a prime example of Muller's Ratchet.


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