scholarly journals FGF signaling acts on different levels of mesoderm development within Spiralia

Development ◽  
2021 ◽  
Author(s):  
Carmen Andrikou ◽  
Andreas Hejnol

FGF signaling is involved in mesoderm induction in members of deuterostomes (e.g. tunicates, hemichordates), but not in flies and nematodes, where it has a role in mesoderm patterning and migration. However, comparable studies in other protostome taxa are missing in order to decipher whether this mesoderm-inducing function of FGF extends beyond the lineage of deuterostomes. Here, we investigated the role of FGF signaling in mesoderm development in three species of lophophorates, a clade within the protostome group Spiralia. Our gene expression analyses show that the mesodermal molecular patterning is overall conserved between brachiopods and phoronids, but the spatial and temporal recruitment of transcription factors differs significantly. Moreover, the use of the inhibitor SU5402 demonstrates that FGF signaling is involved in different steps of mesoderm development, as well as in morphogenetic movements of gastrulation and axial elongation. Our findings suggest that the mesoderm-inducing role of FGF extends beyond the group of deuterostomes.

2020 ◽  
Author(s):  
Carmen Andrikou ◽  
Andreas Hejnol

AbstractFGF signaling is involved in mesoderm induction in deuterostomes, but not in flies and nematodes, where it has a role in mesoderm patterning and migration. However, comparable studies in other protostomic taxa are missing in order to decipher whether this mesoderm-inducing function of FGF extends beyond the lineage of deuterostomes. Here, we investigated the role of FGF signaling during mesoderm development in three species of lophophorates, a clade within the protostome group Spiralia. Our gene expression analyses show that the molecular patterning of mesoderm development is overall conserved between brachiopods and phoronids, but the spatial and temporal recruitment of transcription factors differs significantly. Moreover, inhibitor experiments demonstrate that FGF signaling is involved in mesoderm formation, morphogenetic movements of gastrulation and posterior axial elongation. Our findings suggest that the inductive role of FGF in mesoderm possibly predates the origin of deuterostomes.


2018 ◽  
Author(s):  
Isabelle Schneider ◽  
Jennifer Kreis ◽  
Axel Schweickert ◽  
Martin Blum ◽  
Philipp Vick

AbstractOrgan left-right (LR) asymmetry is a conserved vertebrate feature, which is regulated by left-sided activation of Nodal signaling. Nodal asymmetry is established by a leftward fluid-flow generated at the ciliated LR organizer (LRO). While the role of fibroblast growth factor (FGF) signaling pathways during mesoderm development are conserved, diverging results from different model organisms suggested a non-conserved function in LR asymmetry. Here, we demonstrate that FGF is required during gastrulation in a dual function at consecutive stages of Xenopus embryonic development. In the early gastrula, FGF is necessary for LRO precursor induction, acting in parallel to FGF-mediated mesoderm induction. During late gastrulation, the FGF/Ca2+-branch is required for specification of the flow sensing lateral LRO cells, a function related to FGF-mediated mesoderm morphogenesis. This second function in addition requires input from the calcium channel Polycystin-2. Thus, analogous to mesoderm development, FGF activity is required in a dual role for laterality specification, namely for generating and sensing of leftward flow. Moreover, our data show that FGF functions in LR asymmetric development are conserved across vertebrate species, from fish to mammals.


Development ◽  
1994 ◽  
Vol 120 (2) ◽  
pp. 463-472 ◽  
Author(s):  
C. LaBonne ◽  
M. Whitman

We have examined the role of FGF signaling during activin-mediated mesoderm induction in Xenopus. Using dominant inhibitory mutants of FGF signal transducers to disrupt the FGF-signaling pathway at the plasma membrane or in the cytosol prevents animal cap blastomeres from expressing several mesodermal markers in response to exogenous activin. Dominant inhibitory mutants of the FGF receptor, c-ras or c-raf inhibit the ability of activin to induce molecular markers of both dorsal and ventral mesoderm including Xbra, Mix1 and Xnot. Some transcriptional responses to activin such as goosecoid and Xwnt8 are inhibited less effectively than others, however, suggesting that there may differing requirements for an FGF signal in the responses of mesoderm-specific genes to activin induction. Despite the requirement for this signaling pathway during activin induction, downstream components of this pathway are not activated in response to activin, suggesting that activin does not signal directly through this pathway.


2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Donghong Chen ◽  
Guofeng Zheng ◽  
Qing Yang ◽  
Le Luo ◽  
Jinglian Shen

Abstract Background IL-35 subunit EBI3 is up-regulated in pulmonary fibrosis tissues. In this study, we investigated the pathological role of EBI3 in pulmonary fibrosis and dissected the underlying molecular mechanism. Methods Bleomycin-induced pulmonary fibrosis mouse model was established, and samples were performed gene expression analyses through RNAseq, qRT-PCR and Western blot. Wild type and EBI3 knockout mice were exposed to bleomycin to investigate the pathological role of IL-35, via lung function and gene expression analyses. Primary lung epithelial cells were used to dissect the regulatory mechanism of EBI3 on STAT1/STAT4 and STAT3. Results IL-35 was elevated in both human and mouse with pulmonary fibrosis. EBI3 knockdown aggravated the symptoms of pulmonary fibrosis in mice. EBI3 deficiency enhanced the expressions of fibrotic and extracellular matrix-associated genes. Mechanistically, IL-35 activated STAT1 and STAT4, which in turn suppressed DNA enrichment of STAT3 and inhibited the fibrosis process. Conclusion IL-35 might be one of the potential therapeutic targets for bleomycin-induced pulmonary fibrosis.


2008 ◽  
Vol 237 (5) ◽  
pp. 1243-1254 ◽  
Author(s):  
Russell B. Fletcher ◽  
Richard M. Harland

2020 ◽  
Author(s):  
M. L. Richter ◽  
I.K. Deligiannis ◽  
A. Danese ◽  
E. Lleshi ◽  
P. Coupland ◽  
...  

AbstractSingle-cell RNA-seq reveals the role of pathogenic cell populations in development and progression of chronic diseases. In order to expand our knowledge on cellular heterogeneity we have developed a single-nucleus RNA-seq2 method that allows deep characterization of nuclei isolated from frozen archived tissues. We have used this approach to characterize the transcriptional profile of individual hepatocytes with different levels of ploidy, and have discovered that gene expression in tetraploid mononucleated hepatocytes is conditioned by their position within the hepatic lobe. Our work has revealed a remarkable crosstalk between gene dosage and spatial distribution of hepatocytes.


Development ◽  
1999 ◽  
Vol 126 (24) ◽  
pp. 5621-5634 ◽  
Author(s):  
M. Watanabe ◽  
M. Whitman

We have examined the role of the maternally encoded transcription factor FAST-1 in the establishment of the mesodermal transcriptional program in Xenopus embryos. FAST-1 has been shown to associate with Smad2 and Smad4, transducers of TGFbeta superfamily signals, in response to stimulation by several TGFbeta superfamily ligands. The FAST-1/Smad2/Smad4 complex binds and activates a 50 bp activin responsive element identified in the promoter of the meso-endodermal marker Mix.2. We have now used three complementary approaches to demonstrate that FAST-1 is a central regulator of mesoderm induction by ectopic TGFbeta superfamily ligands and during endogenous patterning: ectopic expression of mutationally activated FAST-1, ectopic expression of dominant inhibitory FAST-1, and injection of a blocking antibody specific for FAST-1. Expression of constitutively transcriptionally active FAST-1 fusion protein (FAST-VP16(A)) in prospective ectoderm can directly induce the same set of general and dorsal mesodermal genes, as well as some endodermal genes, as are induced by activin or Vg1. In intact embryos, this construct can induce secondary axes similar to those induced by activin or Vg1. Conversely, expression of a FAST-1-repressor fusion (FAST-En(R)) in prospective ectoderm blocks induction of mesodermal genes by activin, while expression of FAST-En(R) in intact embryos prevents general/dorsal mesodermal gene expression and axial development. Injection of a blocking antibody specific for FAST-1 prevents induction of mesodermal response genes by activin or Vg1, but not by FGF. In intact embryos, this antibody can prevent the expression of early mesodermal markers and inhibit axis formation, demonstrating that FAST-1 is a necessary component of the first steps in the specification of mesoderm.


2000 ◽  
Vol 89 (1) ◽  
pp. 297-304 ◽  
Author(s):  
Stephen Welle ◽  
Kirti Bhatt ◽  
Charles A. Thornton

To gain a better understanding of the potential role of altered gene expression in the diminished muscle function in old age, we performed a broad search for transcripts expressed at quantitatively different levels in younger (21–24 yr) and older (66–77 yr) human vastus lateralis muscle by serial analysis of gene expression (SAGE). Because SAGE was based on RNA pooled from muscle of several different subjects, relative concentrations of selected mRNAs also were determined in individual muscle samples by quantitative RT-PCR. There were 702 SAGE tags detected at least 10 times in one or both mRNA pools, and the detection frequency was different (at P < 0.01) between young and older muscle for 89 of these. The ratio of myosin heavy chain 2a mRNA to myosin heavy chain 1 mRNA was reduced in older muscle. The mRNAs encoding several mitochondrial proteins involved in electron transport (including several subunits of cytochrome- c oxidase and NADH dehydrogenase) and subunits of ATP synthase were ∼30% less abundant in older muscle. Several mRNAs encoding enzymes involved in glucose metabolism also were less abundant in older muscle. Analysis of individual samples revealed that the differences suggested by SAGE were not artifacts of atypical gene expression in one or a few individuals. These data suggest that some of the phenotypic changes in senescent muscle may be related to altered gene transcription.


2020 ◽  
Vol 11 (1) ◽  
Author(s):  
Shan Li

AbstractThis article studies the role of rainfall in determining the education composition of Mexico-US migration. Emphasizing the relationship between rainfall and migration costs, a revised Roy model indicates that rainfall affects selection on education through not only households’ liquidity constraints but also the comparisons between changes in migration costs and wage differentials at different levels of education. With retrospective data on the migration history of male Mexicans, the empirical analysis shows that the inverted U-shaped relationship between migration probabilities and education is less dispersed with a higher vertex when rainfall decreases, suggesting higher migration costs and reinforced self-selection patterns. The impacts of rainfall on selection and education are stronger for the migrant stock than for migration flows. Studying how rainfall influences migrants’ return decisions provides consistent results.


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