Brahma is essential for Drosophila intestinal stem cell proliferation and regulated by Hippo signaling

Jin, Yunyun; Xu, Jinjin; Yin, Meng‐Xin; Lu, Yi; Hu, Lianxin; Li, Peixue; Zhang, Peng; Yuan, Zengqiang; Ho, Margaret S.; Ji, Hongbin; Zhao, Yun; Zhang, Lei

doi:10.7554/elife.00999

Cited by 65 publications

(77 citation statements)

References 60 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Other co-factors of Yki/YAP that promote transcription include WBP2 (Zhang et al, 2011b), MASK1/2 (Sansores- Garcia et al, 2013;Sidor et al, 2013) and the SWI/SNF complex (Jin et al, 2013;Oh et al, 2013). The activity of Yki was found to be regulated by the Drosophila Hippo-Warts (Hpo-Wts) kinase signalling pathway, in which Wts directly phosphorylates Yki to promote its relocalisation from the nucleus to the cytoplasm (Dong et al, 2007;Huang et al, 2005;Oh and Irvine, 2008).…”

Section: Introductionmentioning

confidence: 99%

Integrin signalling regulates YAP and TAZ to control skin homeostasis

Elbediwy¹,

Vincent‐Mistiaen²,

Spencer‐Dene³

et al. 2016

Journal of Cell Science

View full text Add to dashboard Cite

The skin is a squamous epithelium that is continuously renewed by a population of basal layer stem/progenitor cells and can heal wounds. Here, we show that the transcription regulators YAP and TAZ localise to the nucleus in the basal layer of skin and are elevated upon wound healing. Skin-specific deletion of both YAP and TAZ in adult mice slows proliferation of basal layer cells, leads to hair loss and impairs regeneration after wounding. Contact with the basal extracellular matrix and consequent integrin-Src signalling is a key determinant of the nuclear localisation of YAP/TAZ in basal layer cells and in skin tumours. Contact with the basement membrane is lost in differentiating daughter cells, where YAP and TAZ become mostly cytoplasmic. In other types of squamous epithelia and squamous cell carcinomas, a similar control mechanism is present. By contrast, columnar epithelia differentiate an apical domain that recruits CRB3, Merlin (also known as NF2), KIBRA (also known as WWC1) and SAV1 to induce Hippo signalling and retain YAP/TAZ in the cytoplasm despite contact with the basal layer extracellular matrix. When columnar epithelial tumours lose their apical domain and become invasive, YAP/TAZ becomes nuclear and tumour growth becomes sensitive to the Src inhibitor Dasatinib.

show abstract

Section: Introductionmentioning

confidence: 99%

Integrin signalling regulates YAP and TAZ to control skin homeostasis

Elbediwy¹,

Vincent‐Mistiaen²,

Spencer‐Dene³

et al. 2016

Journal of Cell Science

View full text Add to dashboard Cite

show abstract

“…However, to date, only few studies have investigated chromatin modifiers in the process of regulating ISC behavior in Drosophila (Amcheslavsky et al, 2014;Buszczak et al, 2009;Jin et al, 2013;Ma et al, 2013;Zeng et al, 2013). Nipped-A is the Drosophila homolog of mammalian transformation/transcription domain-associated protein (TRRAP) and yeast Tra1 and is an important subunit of histone acetyltransferase (HAT) complexes such as SAGA and Tip60 (Gause et al, 2006;Kusch et al, 2003;Murr et al, 2007).…”

Section: Introductionmentioning

confidence: 99%

Nipped-A regulates intestinal stem cell proliferation in Drosophila

et al. 2017

View full text Add to dashboard Cite

Adult stem cells uphold a delicate balance between quiescent and active states, a deregulation of which can lead to age-associated diseases such as cancer. In Drosophila, intestinal stem cell (ISC) proliferation is tightly regulated and mis-regulation is detrimental to intestinal homeostasis. Various factors are known to govern ISC behavior; however, transcriptional changes in ISCs during aging are still unclear. RNA sequencing of young and old ISCs newly identified Nipped-A, a subunit of histone acetyltransferase complexes, as a regulator of ISC proliferation that is upregulated in old ISCs. We show that Nipped-A is required for maintaining the proliferative capacity of ISCs during aging and in response to tissue-damaging or tumorigenic stimuli. Interestingly, Drosophila Myc cannot compensate for the effect of the loss of Nipped-A on ISC proliferation. Nipped-A seems to be a superordinate regulator of ISC proliferation, possibly by coordinating different processes including modifying the chromatin landscape of ISCs and progenitors.

show abstract

“…Interestingly, specific chromatin modifiers are important for regeneration in several organisms, suggesting that chromatin modification regulates the expression of at least some regeneration genes. For example, pharmacological inhibition of histone deacetylases blocks Xenopus tail regeneration (Tseng et al, 2011), the H3K27me3 demethylase Kdm6b.1 is required for zebrafish fin regeneration (Stewart et al, 2009), the PRC1 component Bmi1 is required for a regenerative response to pancreatitis in mice (Fukuda et al, 2012), several members of the Set1/MLL family of histone methyltransferases are required for the stem cell-based regeneration that occurs in planaria (Hubert et al, 2014), the SWI/SNF component Brg1 (Smarca4 -Mouse Genome Informatics) is essential for mouse epidermal wound repair and hair regeneration (Xiong et al, 2013) and its Drosophila homolog, Brahma, is important for midgut regeneration (Jin et al, 2013). In most of these cases, however, the extent to which tissue damage induces chromatin modification and the genes regulated by these chromatin modifiers during regeneration remain unknown.…”

Section: Introductionmentioning

confidence: 99%

Trithorax regulates systemic signaling duringDrosophilaimaginal disc regeneration

2015

View full text Add to dashboard Cite

Although tissue regeneration has been studied in a variety of organisms, from Hydra to humans, many of the genes that regulate the ability of each animal to regenerate remain unknown. The larval imaginal discs of the genetically tractable model organism Drosophila melanogaster have complex patterning, wellcharacterized development and a high regenerative capacity, and are thus an excellent model system for studying mechanisms that regulate regeneration. To identify genes that are important for wound healing and tissue repair, we have carried out a genetic screen for mutations that impair regeneration in the wing imaginal disc. Through this screen we identified the chromatin-modification gene trithorax as a key regeneration gene. Here we show that animals heterozygous for trithorax are unable to maintain activation of a developmental checkpoint that allows regeneration to occur. This defect is likely to be caused by abnormally high expression of puckered, a negative regulator of Jun N-terminal kinase (JNK) signaling, at the wound site. Insufficient JNK signaling leads to insufficient expression of an insulin-like peptide, dILP8, which is required for the developmental checkpoint. Thus, trithorax regulates regeneration signaling and capacity.

show abstract

Brahma is essential for Drosophila intestinal stem cell proliferation and regulated by Hippo signaling

Cited by 65 publications

References 60 publications

Integrin signalling regulates YAP and TAZ to control skin homeostasis

Integrin signalling regulates YAP and TAZ to control skin homeostasis

Nipped-A regulates intestinal stem cell proliferation in Drosophila

Trithorax regulates systemic signaling duringDrosophilaimaginal disc regeneration

Contact Info

Product

Resources

About