Otefin, a Nuclear Membrane Protein, Determines the Fate of Germline Stem Cells in Drosophila via Interaction with Smad Complexes

Jiang, Xiaoyong; Xia, Laixin; Chen, Dongsheng; Yang, Yingyue; Huang, Haidong; Yang, Lele; Zhao, Qi; Shen, Lijun; Wang, Jun; Chen, Dahua

doi:10.1016/j.devcel.2008.04.008

Cited by 16 publications

(34 citation statements)

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“…Of note, MAN1, a LEM‐protein that anchors to lamins, was shown to bind R‐Smad proteins and to regulate BMP signaling dynamics . Furthermore, Smad4 binds to the INM‐localized LEM protein Otefin, which regulates Smad4 transcriptional activity . Thus, LEM‐proteins may integrate mechanical signals into the BMP pathway on the nuclear level and regulate signaling in response to nuclear deformation.…”

Section: How Are Mechanical Signals Integrated Into the Bmp Pathway?mentioning

confidence: 99%

BMP growth factor signaling in a biomechanical context

et al. 2013

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Bone Morphogenetic Proteins (BMPs) are members of the transforming growth factor-β superfamily of secreted polypeptide growth factors and are important regulators in a multitude of cellular processes. To ensure the precise and balanced propagation of their pleiotropic signaling responses, BMPs and their corresponding signaling pathways are subject to tight control. A large variety of regulatory mechanisms throughout different biological levels combines into a complex network and provides the basis for physiological BMP function. This regulatory network not only includes biochemical factors but also mechanical cues. Both BMP signaling and mechanotransduction pathways are tightly interconnected and represent an elaborate signaling network active during development but also during organ homeostasis. Moreover, its dysregulation is associated with a number of human pathologies. A more detailed understanding of this crosstalk in respect to molecular interactions will be indispensable in the future, in particular to understand BMP-related diseases as well as with regard to an efficient clinical application of BMP ligands.

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Section: How Are Mechanical Signals Integrated Into the Bmp Pathway?mentioning

confidence: 99%

BMP growth factor signaling in a biomechanical context

et al. 2013

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“…Ote physically interacts with Medea to silence Bam in the GSCs. Over-expression of ote in the germ line cells increased the number of GSCs, implying that it is instructive for stem cell identity [30]. In contrast, bam expression at the tip of nup98-96 2288 /Df(3R)mbc-R1 germaria did not extend into the GSC position, and overexpression of nup98-96 had no effect on GSC number.…”

Section: Discussionmentioning

confidence: 92%

Nucleoporin98-96 Function Is Required for Transit Amplification Divisions in the Germ Line of Drosophila melanogaster

et al. 2011

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Production of specialized cells from precursors depends on a tightly regulated sequence of proliferation and differentiation steps. In the gonad of Drosophila melanogaster, the daughters of germ line stem cells (GSC) go through precisely four rounds of transit amplification divisions to produce clusters of 16 interconnected germ line cells before entering a stereotypic differentiation cascade. Here we show that animals harbouring a transposon insertion in the center of the complex nucleoporin98-96 (nup98-96) locus had severe defects in the early steps of this developmental program, ultimately leading to germ cell loss and sterility. A phenotypic analysis indicated that flies carrying the transposon insertion, designated nup98-962288, had dramatically reduced numbers of germ line cells. In contrast to controls, mutant testes contained many solitary germ line cells that had committed to differentiation as well as abnormally small clusters of two, four or eight differentiating germ line cells. This indicates that mutant GSCs rather differentiated than self-renewed, and that these GSCs and their daughters initiated the differentiation cascade after zero, or less than four rounds of amplification divisions. This phenotype remained unaffected by hyper-activation of signalling pathways that normally result in excessive proliferation of GSCs and their daughters. Expression of wildtype nup98-96 specifically in the germ line cells of mutant animals fully restored development of the GSC lineage, demonstrating that the effect of the mutation is cell-autonomous. Nucleoporins are the structural components of the nucleopore and have also been implicated in transcriptional regulation of specific target genes. The nuclear envelopes of germ cells and general nucleocytoplasmic transport in nup98-96 mutant animals appeared normal, leading us to propose that Drosophila nup98-96 mediates the transport or transcription of targets required for the developmental timing between amplification and differentiation.

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“…For Cy3‐dUTP labeling, the ovaries were incubated in the reagent (1:20 dilution of the terminal deoxynucleotidyl transferase solution) in label solution (nucleotide mixture) for 1 h at 37°C. Fixation and Cy3‐dU detection were described previously (Jiang et al, ).…”

Section: Methodsmentioning

confidence: 99%

“…Notch signaling influences the GSC number via regulating stem cell niche formation in Drosophila ovaries (Song et al, ). In comparison, a much greater number of intrinsic factors that regulate the ovarian GSC fate in Drosophila have been identified, such as bam , nanos , pumilio , fused , otefin , effete , cyclin E and GCN5 (Mckearin and Ohlstein, ; Forbes and Lehmann, ; Chen and Mckearin, ; Jiang et al, ; Chen et al, ; Xia et al, ; Ables and Drummondbarbosa, ; Liu et al, ). In addition, microRNA‐mediated translational repression pathways in adult Drosophila ovaries are essential for GSCs maintenance (Jin and Xie, ; Park et al, ; Yang et al, ).…”

Section: Introductionmentioning

confidence: 99%

Spaghetti, a homolog of human RPAP3 (RNA polymerase II‐associated protein 3), determines the fate of germline stem cells in Drosophila ovary

Chen

Tao

Zhou

et al. 2017

Cell Biology International

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The Drosophila ovary provides an attractive model for studying the extrinsic or intrinsic factors that regulate the fate of germline stem cells (GSCs). Using this model, we identified a new role for Drosophila spaghetti (spag), encoding a homolog of human RNA polymerase II-associated protein 3 (RPAP3), in regulating the fate of ovarian GSCs. Results from spag knockdown and genetic mosaic studies suggest that spag functions as an intrinsic factor for GSCs maintenance. Loss of Spag by, either spag RNAi or null mutation failed to trigger apoptosis in ovarian GSCs. Overexpression of spag led to negligible increases in the number of GSC/Cystoblast (CB) cells, suggesting that an excess of Spag is not sufficient to accelerate the proliferation of GSCs or delay CBs' differentiation. Our study provides evidence supporting that spag is involved in adult stem cells maintenance. In addition, the RNAi screen results showed that knockdown of Hsp90, one of known Spag interacting partners, led to loss of ovarian GSCs in Drosophila. Heterozygous mutations in hsp90 (hsp90/þ) dramatically accelerated the GSC loss in spag RNAi ovaries, suggesting that the Spag-contained complex possibly plays an essential role in controlling the GSCs fate.

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Otefin, a Nuclear Membrane Protein, Determines the Fate of Germline Stem Cells in Drosophila via Interaction with Smad Complexes

Cited by 16 publications

References 0 publications

BMP growth factor signaling in a biomechanical context

BMP growth factor signaling in a biomechanical context

Nucleoporin98-96 Function Is Required for Transit Amplification Divisions in the Germ Line of Drosophila melanogaster

Spaghetti, a homolog of human RPAP3 (RNA polymerase II‐associated protein 3), determines the fate of germline stem cells in Drosophila ovary

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