scholarly journals Geminin Orchestrates Somite Formation by Regulating Fgf8 and Notch Signaling

2018 ◽  
Vol 2018 ◽  
pp. 1-13
Author(s):  
Wei Huang ◽  
Yu Zhang ◽  
Kang Cao ◽  
Lingfei Luo ◽  
Sizhou Huang
Keyword(s):  
Notch Signaling ◽  
Signaling Pathways ◽  
Critical Factor ◽  
Loss Of Function ◽  
Presomitic Mesoderm ◽  
Tail Bud ◽  
Notch Activity ◽  
Somite Formation ◽  
First Time

During somitogenesis, Fgf8 maintains the predifferentiation stage of presomitic mesoderm (PSM) cells and its retraction gives a cue for somite formation. Delta/Notch initiates the expression of oscillation genes in the tail bud and subsequently contributes to somite formation in a periodic way. Whether there exists a critical factor coordinating Fgf8 and Notch signaling pathways is largely unknown. Here, we demonstrate that the loss of function of geminin gave rise to narrower somites as a result of derepressed Fgf8 gradient in the PSM and tail bud. Furthermore, in geminin morphants, the somite boundary could not form properly but the oscillation of cyclic genes was normal, displaying the blurry somitic boundary and disturbed somite polarity along the AP axis. In mechanism, these manifestations were mediated by the disrupted association of the geminin/Brg1 complex with intron 3 of mib1. The latter interaction was found to positively regulate mib1 transcription, Notch activity, and sequential somite segmentation during somitogenesis. In addition, geminin was also shown to regulate the expression of deltaD in mib1-independent way. Collectively, our data for the first time demonstrate that geminin regulates Fgf8 and Notch signaling to regulate somite segmentation during somitogenesis.

The control of somitogenesis in mouse embryos

Development ◽  
1981 ◽  
Vol 65 (Supplement) ◽  
pp. 103-128
Author(s):  
P. P. L. Tam
Keyword(s):  
Body Size ◽  
Primitive Streak ◽  
Mouse Embryos ◽  
The Body ◽  
Whole Body ◽  
Axis Formation ◽  
Presomitic Mesoderm ◽  
Tail Bud ◽  
Somite Formation ◽  
Somitic Mesoderm

Somitogenesis in the mouse embryo commences with the generation of presumptive somitic mesoderm at the primitive streak and in the tail-bud mesenchyme. The presumptive somitic mesoderm is then organized into somite primordia in the presomitic mesoderm. These primordia undergo morphogenesis leading to the segmentation of somites at the cranial end of the presomitic mesoderm. Somite sizes at the time of segmentation vary according to the position of the somite in the body axis: the size of lumbar and sacral somites is nearly twice that of upper trunk somites and of tail somites. The size of the presomitic mesoderm, which is governed by the balance between the addition of cells at the caudal end and the removal of somites at the cranial end, changes during embryonic development. Somitogenesis is disturbed during the compensatory growth of mouse embryos which have suffered a drastic size reduction at the primitive-streak and early-organogenesis stages. The formation of somites is retarded and the upper trunk somites are formed at a smaller size. The embryo also follows an entirely different growth profile, but a normal body size is restored by the early foetal stage. The somite number is regulated to normal and this is brought about by an altered rate of somite formation and the adjustment of somite size in proportion to the whole body size. It is proposed that axis formation and somitogenesis are related morphogenetic processes and that embryonic growth controls the kinetics of somitogenesis, namely by regulating the number of cells allocated to each somite and the rate of somite formation.

scholarly journals Axial skeletal defects caused by mutation in the spondylocostal dysplasia/pudgy geneDll3are associated with disruption of the segmentation clock within the presomitic mesoderm

Development ◽  
2002 ◽  
Vol 129 (7) ◽  
pp. 1795-1806 ◽  
Author(s):  
Sally L. Dunwoodie ◽  
Melanie Clements ◽  
Duncan B. Sparrow ◽  
Xin Sa ◽  
Ronald A. Conlon ◽  
...  
Keyword(s):  
Gene Targeting ◽  
Skeletal Dysplasia ◽  
Null Allele ◽  
Developmental Origins ◽  
Loss Of Function ◽  
Presomitic Mesoderm ◽  
Phenotypic Analysis ◽  
Segmentation Clock ◽  
Skeletal Defects ◽  
Somite Formation

A loss-of-function mutation in the mouse delta-like3 (Dll3) gene has been generated following gene targeting, and results in severe axial skeletal defects. These defects, which consist of highly disorganised vertebrae and costal defects, are similar to those associated with the Dll3-dependent pudgy mutant in mouse and with spondylocostal dysplasia (MIM 277300) in humans. This study demonstrates that Dll3neo and Dll3pu are functionally equivalent alleles with respect to the skeletal dysplasia, and we suggest that the three human DLL3 mutations associated with spondylocostal dysplasia are also functionally equivalent to the Dll3neo null allele. Our phenotypic analysis of Dll3neo/Dll3neo mutants shows that the developmental origins of the skeletal defects lie in delayed and irregular somite formation, which results in the perturbation of anteroposterior somite polarity. As the expression of Lfng, Hes1, Hes5 and Hey1 is disrupted in the presomitic mesoderm, we suggest that the somitic aberrations are founded in the disruption of the segmentation clock that intrinsically oscillates within presomitic mesoderm.

scholarly journals Presomitic mesoderm-specific expression of the transcriptional repressorHes7is controlled by E-box, T-box, and Notch signaling pathways

2018 ◽  
Vol 293 (31) ◽  
pp. 12167-12176 ◽  
Author(s):  
Shinichi Hayashi ◽  
Yasukazu Nakahata ◽  
Kenji Kohno ◽  
Takaaki Matsui ◽  
Yasumasa Bessho
Keyword(s):  
Notch Signaling ◽  
Signaling Pathways ◽  
Presomitic Mesoderm ◽  
Specific Expression ◽  
T Box ◽  
E Box

Expression domains of a zebrafish homologue of the Drosophila pair-rule gene hairy correspond to primordia of alternating somites

Development ◽  
1996 ◽  
Vol 122 (7) ◽  
pp. 2071-2078 ◽  
Author(s):  
M. Muller ◽  
E. Weizsacker ◽  
J.A. Campos-Ortega
Keyword(s):  
Expression Pattern ◽  
Bhlh Protein ◽  
Presomitic Mesoderm ◽  
Tail Bud ◽  
Expression Domain ◽  
Somite Formation ◽  
Pair Rule Gene ◽  
Pair Rule ◽  
Time Point

her1 is a zebrafish cDNA encoding a bHLH protein with all features characteristic of members of the Drosophila HAIRY-E(SPL) family. During late gastrulation stages, her1 is expressed in the epibolic margin and in two distinct transverse bands of hypoblastic cells behind the epibolic front. After completion of epiboly, this pattern persists essentially unchanged through postgastrulation stages; the marginal domain is incorporated in the tail bud and, depending on the time point, either two or three paired bands of expressing cells are present within the paraxial presomitic mesoderm separated by regions devoid of transcripts. Labelling of cells within the her1 expression domains with fluorescein-dextran shows that the cells in the epibolic margin and the tail bud are not allocated to particular somites. However, allocation of cells to somites occurs between the marginal expression domain and the first expression band, anterior to it. Moreover, the her1 bands, and the intervening non-expressing zones, each represents the primordium of a somite. This expression pattern is highly reminiscent of that of Drosophila pair-rule genes. A possible participation of her1 in functions related to somite formation is discussed.

Hyperactivation of RAP1 and JAK/STAT Signaling Pathways Contributes to Fibrosis during the Formation of Nasal Capsular Contraction

2021 ◽  
pp. 1-12
Author(s):  
Meng Wu ◽  
Ming Li ◽  
Hong-Ju Xie ◽  
Hong-Wei Liu
Keyword(s):  
Signaling Pathways ◽  
Type I Collagen ◽  
Ex Vivo ◽  
Capsular Contracture ◽  
Silicone Implant ◽  
Type I ◽  
Loss Of Function ◽  
Sequencing Data ◽  
Functional Changes ◽  
Stat Signaling

Silicone implant-based augmentation rhinoplasty or mammoplasty induces capsular contracture, which has been acknowledged as a process that develops an abnormal fibrotic capsule associated with the immune response to allogeneic materials. However, the signaling pathways leading to the nasal fibrosis remain poorly investigated. We aimed to explore the molecular mechanism underlying the pathogenesis of nasal capsular contracture, with a specific research interest in the signaling pathways involved in fibrotic development at the advanced stage of contracture. By examining our recently obtained RNA sequencing data and global gene expression profiling between grade II and grade IV nasal capsular tissues, we found that both the RAP1 and JAK/STAT signaling pathways were hyperactive in the contracted capsules. This was verified on quantitative real-time PCR which demonstrated upregulation of most of the representative component signatures in these pathways. Loss-of-function assays through siRNA-mediated Rap1 silencing and/or small molecule-directed inhibition of JAK/STAT pathway in ex vivo primary nasal fibroblasts caused a series of dramatic behavioral and functional changes, including decreased cell viability, increased apoptosis, reduced secretion of proinflammatory cytokines, and synthesis of type I collagen, compared to control cells, and indicating the essential role of the RAP1 and JAK/STAT signaling pathways in nasal capsular fibrosis. Our results sheds light on targeting downstream signaling pathways for the prevention and therapy of silicone implant-induced nasal capsular contracture.

scholarly journals Schistosoma mansoni eggs induce Wnt/β-catenin signaling and activate the protooncogene c-Jun in human and hamster colon

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Jakob Weglage ◽  
Friederike Wolters ◽  
Laura Hehr ◽  
Jakob Lichtenberger ◽  
Celina Wulz ◽  
...  
Keyword(s):  
Signaling Pathways ◽  
Colorectal Carcinogenesis ◽  
Sub Saharan Africa ◽  
Interleukin 4 ◽  
Health Burden ◽  
Sub Saharan ◽  
Considerable Morbidity ◽  
First Time

AbstractSchistosomiasis (bilharzia) is a neglected tropical disease caused by parasitic flatworms of the genus Schistosoma, with considerable morbidity in parts of the Middle East, South America, Southeast Asia, in sub-Saharan Africa, and particularly also in Europe. The WHO describes an increasing global health burden with more than 290 million people threatened by the disease and a potential to spread into regions with temperate climates like Corsica, France. The aim of our study was to investigate the influence of S. mansoni infection on colorectal carcinogenic signaling pathways in vivo and in vitro. S. mansoni infection, soluble egg antigens (SEA) and the Interleukin-4-inducing principle from S. mansoni eggs induce Wnt/β-catenin signaling and the protooncogene c-Jun as well as downstream factor Cyclin D1 and markers for DNA-damage, such as Parp1 and γH2a.x in enterocytes. The presence of these characteristic hallmarks of colorectal carcinogenesis was confirmed in colon biopsies from S. mansoni-infected patients demonstrating the clinical relevance of our findings. For the first time it was shown that S. mansoni SEA may be involved in the induction of colorectal carcinoma-associated signaling pathways.

scholarly journals Dominant Enhancers of Egfr in Drosophila melanogaster: Genetic Links Between the Notch and Egfr Signaling Pathways

Genetics ◽  
1997 ◽  
Vol 147 (3) ◽  
pp. 1139-1153 ◽  
Author(s):  
James V Price ◽  
Edward D Savenye ◽  
David Lum ◽  
Ashton Breitkreutz
Keyword(s):  
Notch Signaling ◽  
Signaling Pathways ◽  
Growth Factor Receptor ◽  
Compound Eyes ◽  
Egfr Signaling ◽  
Wing Vein ◽  
Developmental Context ◽  
Epidermal Growth ◽  
Hypomorphic Alleles ◽  
Complex Signaling

The Drosophila epidermal growth factor receptor (EGFR) is a key component of a complex signaling pathway that participates in multiple developmental processes. We have performed and F1 screen for mutations that cause dominant enhancement of wing vein phenotypes associated with mutations in Egfr. With this screen, we have recovered mutations in Hairless (H), vein, groucho (gro), and three apparently novel loci. All of the E(Egfr)s we have identified show dominant interactions in transheterozygous combinations with each other and with alleles of N or Su(H), suggesting that they are involved in cross-talk between the N and EGFR signaling pathways. Further examination of the phenotypic interactions between Egfr, H, and gro revealed that reductions in Egfr activity enhanced both the bristle loss associated with H mutations, and the bristle hyperplasia and ocellar hypertrophy associated with gro mutations. Double mutant combinations of Egfr and gro hypomorphic alleles led to the formation of ectopic compound eyes in a dosage sensitive manner. Our findings suggest that these E(Egfr)s represent links between the Egfr and Notch signaling pathways, and that Egfr activity can either promote or suppress Notch signaling, depending on its developmental context.

scholarly journals Notch signaling coordinates ommatidial rotation in the Drosophila eye via transcriptional regulation of the EGF-Receptor ligand Argos

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Yildiz Koca ◽  
Benjamin E. Housden ◽  
William J. Gault ◽  
Sarah J. Bray ◽  
Marek Mlodzik
Keyword(s):  
Notch Signaling ◽  
Cell Fate ◽  
Planar Cell Polarity ◽  
Egf Receptor ◽  
Control Cell ◽  
Loss Of Function ◽  
Egfr Signaling ◽  
Specific Expression ◽  
Egfr Signaling Pathway ◽  
Ommatidial Rotation

AbstractIn all metazoans, a small number of evolutionarily conserved signaling pathways are reiteratively used during development to orchestrate critical patterning and morphogenetic processes. Among these, Notch (N) signaling is essential for most aspects of tissue patterning where it mediates the communication between adjacent cells to control cell fate specification. In Drosophila, Notch signaling is required for several features of eye development, including the R3/R4 cell fate choice and R7 specification. Here we show that hypomorphic alleles of Notch, belonging to the Nfacet class, reveal a novel phenotype: while photoreceptor specification in the mutant ommatidia is largely normal, defects are observed in ommatidial rotation (OR), a planar cell polarity (PCP)-mediated cell motility process. We demonstrate that during OR Notch signaling is specifically required in the R4 photoreceptor to upregulate the transcription of argos (aos), an inhibitory ligand to the epidermal growth factor receptor (EGFR), to fine-tune the activity of EGFR signaling. Consistently, the loss-of-function defects of Nfacet alleles and EGFR-signaling pathway mutants are largely indistinguishable. A Notch-regulated aos enhancer confers R4 specific expression arguing that aos is directly regulated by Notch signaling in this context via Su(H)-Mam-dependent transcription.

scholarly journals Mesenchymal stem cells regulate maintenance of neural stem cells through VEGFR2 and Notch signaling pathways

Cell Research ◽  
2008 ◽  
Vol 18 (S1) ◽  
pp. S59-S59
Author(s):  
Zhifeng Deng ◽  
Zhumin Liu ◽  
Wei Tu ◽  
Yang Wang ◽  
Yuanlei Lou
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Neural Stem Cells ◽  
Notch Signaling ◽  
Signaling Pathways

scholarly journals MFng Is Dispensable for Mouse Pancreas Development and Function

2009 ◽  
Vol 29 (8) ◽  
pp. 2129-2138 ◽  
Author(s):  
Per Svensson ◽  
Ingela Bergqvist ◽  
Stefan Norlin ◽  
Helena Edlund
Keyword(s):  
Cell Differentiation ◽  
Notch Signaling ◽  
Pancreas Development ◽  
Loss Of Function ◽  
Pancreatic Cell ◽  
Targeted Deletion ◽  
Mouse Pancreas ◽  
Pancreatic Progenitor ◽  
Pancreatic Progenitor Cells ◽  
And Function

ABSTRACT Notch signaling regulates pancreatic cell differentiation, and mutations of various Notch signaling components result in perturbed pancreas development. Members of the Fringe family of β1,3-N-acetylglucosaminyltransferases, Manic Fringe (MFng), Lunatic Fringe (LFng), and Radical Fringe (RFng), modulate Notch signaling, and MFng has been suggested to regulate pancreatic endocrine cell differentiation. We have characterized the expression of the three mouse Fringe genes in the developing mouse pancreas between embryonic days 9 and 14 and show that the expression of MFng colocalized with the proendocrine transcription factor Ngn3. In contrast, the expression of LFng colocalized with the exocrine marker Ptf1a, whereas RFng was not expressed. Moreover, we show that expression of MFng is lost in Ngn3 mutant mice, providing evidence that MFng is genetically downstream of Ngn3. Gain- and loss-of-function analyses of MFng by the generation of mice that overexpress MFng in early pancreatic progenitor cells and mice with a targeted deletion of MFng provide, however, evidence that MFng is dispensable for pancreas development and function, since no pancreatic defects in these mice were observed.

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